Helminths

Helminths (/ˈhɛlmɪnθs/) are a polyphyletic group of eukaryotic parasites.^[1] They are worm-like organisms living in and feeding on 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 and other animals.

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

Categorization

Hookworms attached to the intestinal mucosa

Two pinworms

Helminths is a polyphyletic group of morphologically similar organisms, consisting of members of the following taxa: monogeneans, cestodes (tapeworms), nematodes (roundworms), and trematodes (flukes). The following table shows the principal morphological distinctions for each of these helminth families:

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

Acquisition

Helminths often find their way into a host through contaminated food or water, soil, mosquito bites, and even sexual acts. Poorly washed vegetables eaten raw may contain eggs of nematodes such as Ascaris, Enterobius, Trichuris, and/or cestodes such as Taenia, Hymenolepis, and Echinococcus. Plants may also be contaminated with fluke metacercaria (e.g. Fasciola). Undercooked meats may transmit Taenia (pork, beef and venison), Trichinella (pork and bear), Diphyllobothrium (fish), Clonorchis (fish), and Paragonimus (crustaceans). Schistosomes and nematodes such as hookworms (Ancylostoma and Necator) and Strongyloides can penetrate the skin. Finally, Wuchereria, Onchocerca, and Dracunculus are transmitted by mosquitoes and flies.

Populations in the developing world are at particular risk for infestation with parasitic worms. Risk factors include inadequate water treatment,^[2] use of contaminated water for drinking, cooking, irrigation and to wash food, undercooked food of animal origin, and walking barefoot. Simple measures can have strong impacts on prevention. These include use of shoes, soaking vegetables with 1.5% bleach, adequate cooking of foods, and sleeping under mosquito-proof nets.

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 viral and bacterial infections.

Intestinal helminths

Intestinal helminths, a type of intestinal parasites, reside in the human gastrointestinal tract. They represent one of the most prevalent forms of parasitic disease. Scholars estimate over a quarter of the world’s population is infected with an intestinal worm of some sort, with roundworms, hookworms, and whipworms infecting 1.47 billion people, 1.05 billion people, and 1.30 billion people, respectively.^[3] Furthermore, the World Bank estimates 100 million people may experience stunting or wasting as a result of infection.^[4]

Because of their high mobility and lower standards of hygiene, school-age children are particularly vulnerable to these parasites.^[5] Overall, an estimated 400 million, 170 million, and 300 million children are infected with roundworm, hookworm, and whipworm, respectively.^[6] Children may also be particularly susceptible to the adverse effects of helminth infections due to their incomplete physical development and their greater immunological vulnerability.^[5]

Costs of intestinal helminth infection

Symptoms

In patients with a heavy worm load, infection is frequently symptomatic. Conditions associated with intestinal helminth infection include intestinal obstruction, insomnia, vomiting, weakness, and stomach pains,^[7] and the natural movement of worms and their attachment to the intestine may be generally uncomfortable for their hosts.^[3] The migration of Ascaris larvae through the respiratory passageways can also lead to temporary asthma and other respiratory symptoms.^[7]

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 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.^[8]

Also, the immune response triggered by helminth infection may drain the body’s ability to fight other diseases, making affected individuals more prone to coinfection.^[3] Reasonable evidence indicates helminthiasis is responsible for the unrelenting prevalence of AIDS and tuberculosis in developing, particularly African, countries.^[9] A review of several data clearly revealed the effective treatment of helminth infection reduces HIV progression and viral load, most likely by improving helminth-induced immune suppression.^[10]

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.^[8] This relationship is particularly alarming because it is gradual and often relatively asymptomatic.^[11]

Parasite infection may affect nutrition in several ways. Some scholars argue worms may compete directly with their hosts for access to nutrients; both whipworms^[6] and roundworms^[4] are believed to impact their hosts in this way. Nonetheless, 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.^[3]

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,^[12] amino acid, and fat malabsorption.^[8] Impaired nutrient uptake may result from direct damage to the intestines' 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.^[13] Alternatively, the worms’ release of protease inhibitors to defend against the body’s digestive process may impair the breakdown of other nutritious substances, as well.^[3][6] 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.^[8]

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,^[4] with a recent study of 459 children in Zanzibar reporting even mothers noticed spontaneous increases in appetite after their children underwent a deworming regimen.^[14] Although the exact cause of such anorexia is not known, researchers believe it may be a side effect of body’s immune response to the worm and the stress of combating infection.^[3] Specifically, some of the cytokines released in the immune response have been tied to anorexic reactions in animals.^[6]

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 hosts. 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.^[8] One scholar went so far as to predict, “the blood loss caused by hookworm was equivalent to the daily exsanguination of 1.5 million people”,^[3] while a study in Zanzibar showed a 15¢ triannual application of mebendazole could avert 0.25 l of blood loss per child per year. 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.^[3][8]

The connection between worm burden and malnutrition is further supported by studies indicating deworming programs lead to sharp increases in growth; the presence of this result even in older children has led some scholars to conclude, “it may be easier to reverse stunting in older children than was previously believed.”^[4]

Delayed intellectual development

Once the links between helminth infection and various forms of malnutrition are established, a number of pathways of 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; 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.^[6] 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”.^[8]

These connections are supported by a number of deworming studies. For example, using 47 students from the Democratic Republic of the Congo, 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.^[15] This result may be because 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.^[15]

A number of papers take the study of intestinal helminth beyond the malnutrition-cognition link to focus on the connections between worm infections and memory formation. For example, 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.^[16] Nokes’ optimistic conclusion that “whipworm infection['s]...adverse effect on certain cognitive functions...is reversible by therapy” is particularly significant because it suggests 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.^[16]

The studies of Ezeamama et al. (2005) and Sakti et al. (1999) 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 “undernutrition is not the primary mediator of the observed relationships”^[17] between worm infection and intellectual performance, particularly because their findings were significant in aspects of intellect that went beyond mere cognition and reaction time.^[18]

Finally, 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.”^[3] While they find little evidence this adaptation would provide benefits in the form of energy conservation, the active course of ongoing parasitic disease clearly 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.”^[6] 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, deworming programs improve school attendance by 25% without affecting test outcomes at all.^[19] Nonetheless, these effects may also be related; 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.^[20]

Prevention and control

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.^[3] 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.”^[20] 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."^[20]

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.’^[3]

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. They allow health policymakers to take advantage of existing infrastructure and institutions for the dispensation of medical treatment. Furthermore, students already plan to attend school on a somewhat regular basis, and can be educated about the importance of deworming.

School deworming programs have also been shown to have strong positive externalities. A difference-in-difference model proved the deworming programs in some schools reduced the burden of disease in neighboring, untreated schools; deworming children also has strong benefits for adult infection rates, since children are a significant source of transmission.^[21]

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 such as albendazole is a cheap, safe intervention that is not particularly specific, so can be used fairly effectively against all three of the main intestinal helminths (or any coinfection of them).^[4] Finally, because these worms cannot replicate inside 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.^[21]

Use in medicine

Parasitic worms have been used as a medical treatment for various diseases, particularly those involving an overactive immune response.^[22] As humans have evolved with parasitic worms, proponents argue they are needed for a healthy immune system.^[22] Scientists are looking for a connection between the prevention and control of parasitic worms and the increase in allergies such as hay-fever in developed countries.^[22] 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.^[22] This may be one mechanism for their proposed medicinal effect.

One study suggests 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 work suggests 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 to induce metabolic syndrome, and then injected them with helminths. Helminth infestation improved the rodents' metabolism.^[23] 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 infections by ubiquitous intestinal parasites….^[23]

References

Notes

External links

• Parasitic Roundworm Diseases
• WHO