OVERVIEW: What every clinician needs to know
Parasite name and classification
Nematodes (roundworms) are non-segmented worms (helminths) with elongate cylindrical bodies. Although numerous nematodes infect humans, six spend the majority of their lifecycle in the bowel lumen and are classified as intestinal nematodes: Ascaris lumbricoides; Trichuris trichiura (whipworm); Ancylostoma duodenale and Necator americanus (the two human hookworms); Enterobius vermicularis (pinworm); and Strongyloides stercoralis. Ascaris, Trichuris, and hookworms are commonly grouped together as the soil-transmitted helminths (STHs) due to a shared aspect of their life cycles.
What is the best treatment?
The treatment of choice for intestinal nematodes, with the exception of Strongyloides, is albendazole or mebendazole.
Single-dose or short-course regimens with these oral agents (albendazole 400mg once or mebendazole 500mg once, or 100mg BID for 3 days) cure more than 90% of Ascaris infections.
For Trichuris infections, at least 3-7 days of albendazole (400mg BID) or mebendazole (100mg BID) should be used, because single-dose cure rates are low. Preliminary data suggest that mebendazole may be slightly superior to albendazole for whipworm and that combination therapy with ivermectin may be superior to albendazole or mebendazole monotherapy.
For hookworm, single-dose albendazole (400mg) is preferred over single-dose mebendazole (500mg).
For pinworm (Enterobius), single-dose therapy with albendazole (400mg) or mebendazole (100mg) is highly effective. Household and other close contacts should also be treated, and a second treatment dose is recommended 2 weeks after the first dose because of high re-infection rates and the frequent occurrence of autoinfection.
The preferred treatment for uncomplicated strongyloidiasis is oral ivermectin (200mcg/kg daily for 2 days), which cures 70-85% of chronically infected patients. Strongyloides also causes disseminated disease (hyperinfection syndrome) in certain hosts. Ivermectin is also the preferred treatment for hyperinfection/disseminated strongyloidiasis, usually in prolonged courses (e.g. until ≥7-14 days after clearance of the parasite). Although still experimental, several patients with disseminated strongyloidiasis have been treated successfully with parenteral ivermectin (veterinary formulations). Patients have also been successfully treated with the combination of ivermectin and albendazole.
Although the mechanism is not clear, resistance to albendazole and mebendazole may be developing among the STHs, given the decreasing efficacy of treatment campaigns observed in some areas. Although resistance to ivermectin has been noted in some veterinary parasites, resistance has not been reported in medically important parasites, such as Strongyloides.
Although alternative antiparasitic drugs are available, none are superior to albendazole or mebendazole for all of the intestinal helminths. Pyrantel pamoate (11mg/kg single dose, maximum 1g) is an alternative for Ascaris and hookworm, and ivermectin (200mcg/kg once for Ascaris and 200 mcg/kg QD for 3 days for Trichuris) is an alternative for Ascaris and whipworm. Nitazoxanide appears to be a treatment option for Ascaris and whipworm. For Enterobius infections, alternatives include single-dose ivermectin (200mcg/kg) or pyrantel pamoate (11mg/kg, maximum 1g).
Alternatives for chronic strongyloidiasis include albendazole (400mg BID for 10-14 days) or thiabendazole (25mg/kg BID for 3-7 days), although ivermectin is preferred; thiabendazole is poorly tolerated and less effective, and albendazole has the lowest efficacy of these drugs.
What are the clinical manifestations of infection with these organisms?
Most people infected with Ascaris are asymptomatic, although a small proportion develop cough during the initial phase of infection, when Ascaris larvae are migrating through the lungs (usually about 1-2 weeks after infection). Eosinophilia and eosinophilic pneumonia may accompany this. During chronic infection, adult worms in the small intestinal lumen often provoke no symptoms or produce only mild abdominal pain or nausea. However, heavier infections can adversely affect the nutritional status, intellectual development and growth of children, especially in areas in which malnutrition is common.
Trichuriasis is also usually asymptomatic, although some patients may have eosinophilia. With heavy infections, chronic abdominal pain and diarrhea can result, and stools may have an acrid smell; anemia, growth retardation and clubbing can also occur, particularly in children.
Most people infected with hookworm harbor light infections and are asymptomatic. Initial infection may be characterized by ground itch, a pruritic maculopapular rash at the site of larval skin penetration, seen mostly in previously sensitized individuals. If Migration of larvae through the lungs shortly after infection occurs it may provoke pneumonitis, which is less common and less severe than with Ascaris. Epigastric pain, diarrhea and anorexia may occur about 6-12 weeks after skin penetration, as larvae begin attaching to the small bowel mucosa.
When infection with A. duodenale occurs orally, the early migration of larvae can cause Wakana disease, which is characterized by nausea, vomiting, pharyngeal irritation, cough, dyspnea, and hoarseness. There are important clinical differences between the two hookworm species: N. americanus removes less blood (0.03 ml/day vs. 0.20 ml/day), and produces fewer eggs (5,000-10,000 vs. 10,000-30,000 per day) than A. duodenale. Larvae of the latter can enter a stage of arrested development (including within humans), which may allow A. duodenale to persist in environmental conditions that would otherwise be too harsh. Infants can also be infected by A. duodenale, possibly transplacentally, but most likely through breast milk.
Some infected with adult hookworms experience chronic abdominal pain and eosinophilia. However, the most important manifestations of hookworm disease are iron-deficiency anemia and malnutrition. The anemia from hookworm infection is particularly detrimental to children and pregnant women. A major health problem throughout the developing world, hookworm can impair physical, cognitive, and intellectual growth in children, diminish productivity of workers, and threaten the outcome of pregnancy for mother and child. Higher egg burdens are associated with lower hemoglobin levels, independent of other factors, such as concomitant malaria infection.
Although most pinworm infections are asymptomatic, perianal pruritis can be severe. Other symptoms sometimes associated with pinworm infection include insomnia, nausea, vomiting, abdominal pain, and possibly appendicitis.
Chronic S. stercoralis infections are usually asymptomatic, or cause only mild symptoms. Shortly after infection, some patients develop a localized, erythematous, pruritic rash. Pulmonary symptoms and eosinophilia may appear several days later; diarrhea and abdominal pain may follow. Migrating larvae may produce larva currens, a serpiginous, erythematous, track-like rash. Some chronically infected patients note nausea, diarrhea, epigastric pain, and possibly malabsorption. Chronic strongyloidiasis is not generally associated with pulmonary symptoms.
Do other diseases mimic the manifestations of these diseases?
Although the largely nonspecific manifestations of intestinal nematodes can be mimicked by many disease processes, other intestinal parasitic diseases can mimic intestinal nematode infections and warrant further discussion. These include intestinal cestodes (tapeworms) and trematodes (flatworms).
The intestinal cestodes (e.g., Taenia saginata, T. solium, Diphyllobothrium latum) are segmented, ribbon-like, large worms, often several centimeters (or even meters) in length, which reside in the bowel lumen. The intestinal forms of these helminths can be asymptomatic or can mimic some symptoms of intestinal nematode infection (e.g., abdominal pain, nausea, malaise). Passage of tapeworm proglottids in the stool can occur, although these appear macroscopically different from nematodes. Ascaris is the only intestinal nematode large enough to potentially be confused with intestinal cestodes, but Ascaris is non-segmented and tapeworms are segmented.
More than 60 flukes infect the human intestinal tract. The best known are Fasciolopsis buski, Heterophyes heterophyes, Metagonimus yokogawai, and several Echinostoma species. Most cases occur in Asia, but foci also occur in Africa and the Middle East; all intestinal flukes are foodborne. Infection with intestinal flukes is generally asymptomatic, but abdominal pain or malaise can occur, and these nonspecific symptoms could mimic intestinal nematode infections.
Capillariasis is caused primarily by Capillaria philippinensis, an avian parasite that humans acquire through consumption of freshwater fish, which serve as intermediate hosts. It is endemic primarily to Southeast Asia and some parts of the Middle East. The parasite inhabits the small bowel of humans, causing diarrhea and malabsorption; fever and eosinophilia uncommonly occur. As the only other helminth (in addition to Strongyloides) that can multiply in humans, this nematode can result in an overwhelming infection and, thus, mimic (to some degree) the Strongyloides hyperinfection syndrome.
What laboratory studies should you order and what should you expect to find?
Results consistent with the diagnosis
The diagnosis of intestinal helminth infections is made primarily by microscopic identification of eggs, with the exception of Strongyloides. Stool examinations are very sensitive for the detection of Ascaris, given the high daily egg output of this parasite. Trichuriasis and hookworm infections can also usually be diagnosed by stool examinations, although concentration techniques may be necessary for light infections because the egg output is not as high as with Ascaris. Stool samples may be negative for all of these STHs until 1-3 months after infection occurs. Larvae can sometimes be found in respiratory secretions of patients infected with Ascaris or hookworm during the early migratory phase of infection.
Enterobius eggs are best identified by microscopic examination of adhesive cellophane tape applied to the perianal region (best done early in the morning); eggs are not generally seen in stool. Serologic assays are rarely used to diagnose the STHs or pinworm and are used more frequently in epidemiologic studies.
The diagnosis of uncomplicated strongyloidiasis is confirmed by finding rhabditiform larvae in microscopic stool examination; it is uncommon to find eggs in the stool. However, because relatively few larvae are shed, the sensitivity of a single stool examination is only about 30%; multiple samples should, therefore, be examined (with concentration techniques). Examination of up to seven stool samples can significantly increase sensitivity. Sampling duodenal fluid or small bowel biopsy can increase sensitivity, but practical issues limit usefulness. Placing stool samples on agar plates to observe tracks left by the motile larvae may be the most sensitive method among the stool examination techniques.
Because of these difficulties with microscopy, serologic tests, such as the enzyme-linked immunoassay offered by the Centers for Disease Control and Prevention (CDC; Atlanta, GA), which are more sensitive and are often favored for the diagnosis of strongyloidiasis. The entamoeba stool antigen (EIA) is about 95% sensitive in stool-positive patients, although specificity is lower because of cross-reactivity with other helminths. The titer of Strongyloides antibodies in infected patients generally begins to decline about 6-12 months after cure, as does the peripheral eosinophil count. In contrast to chronic strongyloidiasis, hyperinfection/disseminated strongyloidiasis is often diagnosed by microscopic examination of stool, respiratory, or other specimens, which typically contain many filariform larvae.
Although about 75% of patients chronically infected with Strongyloides have eosinophilia, it is usually low-grade (5-15% of the differential). Patients infected with the STHs also may have low-grade eosinophilia, although it is much less common in chronically infected patients and is more frequently seen in the early, migratory phase of infection. Eosinophilia is uncommon with pinworm infection.
What imaging studies will be helpful in making or excluding the diagnosis of helminthic infection?
At times, Ascaris worms may be seen radiographically (given their large size), in contrast radiographs of the bowel, although this is not a primary means of diagnosis. The other intestinal nematodes are generally not diagnosed radiographically, although all intestinal nematodes may be diagnosed endoscopically.
What complications can be associated with these parasitic infections, and are there additional treatments that can help to alleviate these complications?
Complications of chronic ascariasis are largely mechanical, stemming from the presence of the large adult worms; these can rarely include intestinal, biliary, or pancreatic obstruction, appendicitis, and intestinal perforation. Occasionally, adult worms can pass per rectum, through the nose, or through tear ducts.
Complications of whipworm infection include the Trichuris dysentery syndrome, characterized by tenesmus and frequent stools containing mucus and blood. Recurrent rectal prolapse is a classic complication of whipworm, with adult worms often visible.
Anemia caused by hookworms contributes to 60,000 deaths annually worldwide, and hookworms cause the greatest morbidity and mortality of the soil-transmitted helminths globally.
Heavy Strongyloides infections can rarely cause bowel obstruction, and there has been a report linking S. stercoralis infection and biliary cancer although this observation requires confirmation. The most important complication of Strongyloides is the hyperinfection syndrome that can occur in certain hosts. When this occurs, the intestines and lungs harbor many larvae, and diarrhea is common. Larvae can disseminate widely, sometimes involving the central nervous system (CNS). Eosinophilia is often absent during hyperinfection. Other gastrointestinal manifestations are common, including abdominal pain, vomiting, and intestinal obstruction. Hemorrhage, peritonitis or bacteremia can occur. Pneumonitis is common, with cough, respiratory failure, and diffuse interstitial infiltrates or consolidation on radiographs; respiratory secretions often contain the parasite. Central nervous system (CNS) invasion may cause meningitis and brain abscesses, with larvae in the cerebrospinal fluid or tissue. An association with SIADH has been reported.
Because of the risk of hyperinfection syndrome, all persons infected with Strongyloides should be treated. Given the high prevalence in many areas and the lifelong persistence of this parasite (in the absence of treatment), screening for strongyloidiasis should be considered in persons with any history of exposure to endemic areas.
What are the life cycles of these parasites, and how do these life cycles explain infection in humans?
The life cycles of the four STH species are similar, although Ascaris and Trichuris are primarily transmitted orally, whereas hookworms are acquired primarily through skin in contact with infested soil. The soil-transmitted helminths do not reproduce in humans.
Adult Ascaris worms are typically white or pink, non-segmented, 15-45cm long, and live in the small intestine (see Figure 1). Eggs are thick-shelled, oval, and about 65 × 45µm (see Figure 2). Eggs are passed in the feces of infected persons; once they reach a favorable environment (warm, moist soil), they become infectious after an interval dependent on temperature (e.g. 10-14 days at 30°C or 6 weeks at 17°C). Humans usually acquire the infection by ingesting these eggs via contaminated food or water; eggs then hatch in the small intestine and release larvae that penetrate the intestine and migrate to the lungs a few days later. Over the following week or so, they ascend the tracheobronchial tree, are swallowed, and return to the intestines where they mature into adult worms (see Figure 3). Egg production begins approximately 2 months after infection, and adult worms live 1-2 years. Each adult female worm can produce more than 200,000 eggs per day.
T. trichiura is also known as the whipworm because of its long, whip-like head that embeds into the intestinal mucosa. Adult worms are gray or pink and 3-5cm long (see Figure 4). They primarily reside in the proximal colon; with heavy infections, the distribution can extend to the entire colon. Eggs have a distinctive barrel-shaped appearance with a thick shell, bipolar plugs, and average 50 by 20µm in size (see Figure 5). Eggs shed in the feces become infective under appropriate (moist and shady) conditions, after about 2-4 weeks on soil. After infectious eggs have been ingested by a human, larvae emerge and move to the cecum. Here they molt, embed in the epithelium, and mature into adults (see Figure 6). Oviposition begins 2-3 months after infection, and adults live 1-3 years. Female worms can produce up to 20,000 eggs per day.
The human hookworms A. duodenale and N. americanus are small, gray-white worms about 0.7-1.3cm long and live in the upper small intestine. The ovoid, thin-shelled eggs of the two species are identical and measure about 60 by 40µm (see Figure 7). As with the other STHs, eggs passed in the stool of infected persons must develop on soil (ideally warm, moist, and shady); they hatch there within 1-2 days, becoming larvae (see Figure 8). Larvae then molt over 5-10 days, subsequently becoming infectious. Following contact with human skin, larvae enter the body and are carried to the lungs. They then move up the trachea, are swallowed, and migrate to the small intestine (see Figure 9). Females start egg deposition 4-6 weeks after infection. Although N. americanus can only be transmitted via this percutaneous route, A. duodenale can also be transmitted orally. The adult lifespan averages 3-5 years for N. americanus and 1 year for A. duodenale.
E. vermicularis adult females are small, white roundworms, 9-12mm long (see
Figure 10), although eggs are the life cycle stage most readily identified for diagnosis. They are 50 by 25μm and ovoid, characteristically flattened on one side, and bean-shaped (see Figure 11). Enterobius adults live in the proximal colon of infected patients; females migrate to the perianal region and lay eggs (>10,000 daily per adult female), which stick to the skin and can provoke intense pruritis, facilitating fecal-oral transfer of eggs. About 6 hours after oviposition, the eggs become infectious. Transmission occurs mainly from person-to-person, often via fecal-oral contamination of hands, as well as sexually or through fomites, such as bedding. Ingestion of the eggs then perpetuates the cycle, with larvae hatching from the ingested eggs, migrating to the ileocecal region, and molting into adults (see Figure 12). The lifespan of adult females is 4-10 weeks (adult males live only 2 weeks), and the minimal interval between egg ingestion and subsequent oviposition in the new host is 3-4 weeks.
The life cycle of S. stercoralis alternates between free-living and parasitic cycles, and includes adult worms, two different larval stages, and eggs. These cycles form the basis for autoinfection and multiplication within the host, features relatively unique among the helminths to Strongyloides. Soil-living adult worms produce eggs, which give rise to non-infective rhabditiform larvae. These either continue the free-living cycle by maturing into adults or become infective filariform larvae (see Figure 13). Filariform larvae can penetrate intact human skin, after which they migrate to the lungs. From there, they are expectorated, swallowed, and reach the small intestine; this journey takes about 3-4 weeks. In the intestine, S. stercoralis matures into adult worms, which are semi-translucent and about 2mm long. These produce eggs, which hatch and become rhabditiform larvae.
Although most of these larvae exit the gastrointestinal tract via the stool and subsequently develop into adult worms in the soil, a small number directly become infective (filariform) larvae within the gut and penetrate the intestinal mucosa or perianal skin, completing the life cycle without leaving the host (see Figure 14). This is termed autoinfection, and distinguishes S. stercoralis from nearly all other helminths in several ways, including indefinite persistence in a host (in the absence of treatment), multiplication in the absence of exogenous re-infection, and potential person-to-person transmission.
The geographic distribution of the STHs is determined primarily by sanitation and climate. Eggs and larvae become infective on warm, moist soil; the tropics are, thus, well-suited for transmission, and, because eggs are spread via feces, areas with poor hygiene have the highest transmission rates. Sanitation therefore plays an important role in determining the degree of environmental contamination with eggs. Many developing countries share both the environmental and climatic conditions necessary for transmission; although most are tropical, some temperate countries sustain transmission, albeit seasonally (highest during the warm/rainy season). The use of human excrement to fertilize crops (“night soil”) can also lead to high infection rates. In endemic areas, the prevalence is commonly as high as 80%. Ascaris transmission is particularly robust, given the enormous daily egg output and environmental resistance of these eggs. Ascaris eggs can remain viable for more than 5 years in moist, loose soil and can survive desiccation and freezing temperatures.
The epidemiology of hookworm infection differs slightly from that of Ascaris and whipworm. Necator americanus is the predominant hookworm worldwide. Hookworm infection also occurs in tropical and subtropical areas, given the requirement for a warm, moist climate. The highest prevalence of hookworm occurs in sub-Saharan Africa, followed by China and Southeast Asia. Unlike Ascaris and Trichuris, hookworm prevalence is not exaggerated in urban slums and, instead, occurs mostly in poor, tropical, coastal communities and agrarian communities. Larval development is more susceptible to climatic extremes (low rainfall or temperature) than the eggs of Ascaris.
A. lumbricoides and T. trichiura do not appear to occur in areas where temperatures exceed 37-40°C. However, hookworm occurs throughout many such areas, suggesting that hookworm tolerates higher temperatures than A. lumbricoides and T. trichiura. In the tropics, hookworm is generally confined to coastal plains below 150 meters elevation. Above these altitudes, low temperatures (<20°C) usually limit transmission. Because A. duodenale larvae can undergo arrested development within humans, it can thrive in some areas where N. americanus cannot; this may allow A. duodenale to survive cold winter months.
Hookworms are unable to survive desiccation, and a minimum amount of rainfall is also an important determinant influencing hookworm transmission. In some endemic areas in which hookworm transmission is seasonal, new infections with A. duodenale can appear 8-10 months after the rainy season, following emergence of larvae from this arrested development stage. Soil type is another environmental factor important for hookworm transmission. Sandy soils facilitate the migration of infective larvae, whereas clay soils inhibit migration, another reason hookworm is most prevalent in coastal areas where sandy soils predominate.
Enterobius transmission is favored wherever there is poor sanitation, overcrowding, and lack of water. Because Strongyloides transmission occurs via skin contact with fecally-contaminated soil, transmission is favored where poor hygienic conditions are combined with a warm, moist climate.
Soil-transmitted helminths are among the most common of human parasites. Not only are more than 1 billion people infected by at least one of these worms, many are infected with multiple species. Approximately 1 billion people are infected with Ascaris (the most common helminth infection of humans), about 800 million with Trichuris, and 700 million with hookworm. Mortality attributed to Ascaris is estimated at more than 60,000 people per year, and more than 15% of infected people suffer morbidity. Although widely distributed, ascariasis is most abundant in the tropics. Most cases of STH infections in non-endemic regions occur among immigrants and travelers. Infections in such persons generally resolve within a few years even without treatment when the adult worms die. Because of the requirement that STH eggs or larvae develop on soil before becoming infectious, these parasites cannot be transmitted directly from person-to-person and cannot multiply in the host. This contrasts, for example, with Strongyloides (and pinworm), which can be transmitted from person-to-person.
Enterobiasis is also highly prevalent, with global prevalence rates that approach that of the STHs. Unlike other intestinal nematodes, pinworm infection occurs worldwide and does not disproportionately affect residents of tropical countries. Pinworm is the most common helminth infection in the United States.
Global estimates of strongyloidiasis prevalence vary widely, from 3-100 million infected; S. stercoralis is less common than the other major intestinal nematodes. Strongyloidiasis is found throughout the tropics and subtropics and in limited foci of the United States (e.g. Appalachia) and Europe. In developing countries, strongyloidiasis prevalence rates can be striking, for example, 25% in Thailand and Nigeria, 28% in Brazil, and 40% in Colombia. Most infections in developed countries are imported; for example, prevalence rates in resettled US refugees can be high, with one recent study reporting 46% S. stercoralis seroprevalence in a group of resettled Sudanese refugees. Another study found that 39% of asymptomatic refugees in Boston with eosinophilia were S. stercoralis seropositive. Given the high prevalence in many tropical and subtropical areas and the lifelong persistence of this parasite in the absence of treatment, physicians should consider strongyloidiasis both in persons with recent exposure to endemic areas and immigrant or refugee patients in developed countries even if they immigrated decades earlier.
For both Ascaris and Trichuris, children in impoverished rural areas are particularly heavy amplifiers of these infections, as they often play on contaminated soil and more frequently are exposed by hand-to-mouth behaviors. The highest prevalence rates are typically seen in those younger than 10 years of age, with prevalence decreasing in older persons. Even in highly endemic areas, most infected people harbor only a small number of worms; only a minority (usually children) is heavily infected. Children, therefore, account for the majority of the worms in a community and most of the eggs that are shed into the environment.
Unlike Ascaris and Trichuris, hookworm prevalence most commonly increases throughout childhood and then plateaus in young adulthood.
Well-recognized risk factors for Enterobius infection include overcrowding, poor sanitation, and lack of water for bathing and washing of hands and clothes.
In developed countries, such as the United States, Strongyloides transmission occurs (rarely) in the Southeast (Appalachia), although the highest seroprevalence rates are seen in the institutionalized, the poor, or in rural areas. In developed settings, Strongyloides infection is most commonly seen in immigrants from more highly endemic countries. Among those infected with Strongyloides, certain patient populations are more susceptible to the hyperinfection syndrome; this includes those receiving corticosteroids or cancer chemotherapeutic agents, those co-infected with HTLV, as well as other immunosuppressive conditions. Patients with HTLV infection also seem more susceptible to Strongyloides infection itself.
In areas with good control programs, such as mass drug administration (MDA), sanitation initiatives, and promotion of good footwear, substantial decreases in the prevalence of the STHs has been seen. Large-scale control programs for pinworm and Strongyloides have been scarcer. However, the prevalence of pinworm in well-recognized at-risk groups, such as residents of orphanages and homes for the intellectually disabled, appears in decline. This likely reflects improved sanitation and living standards in such institutions. Studies based on stool examination in the 1960s and 1970s showed Strongyloides prevalence rates of 0.5-4.0% in differing US cohorts, mostly in the Southeast and Appalachia, although prevalence has subsequently decreased.
No accepted guidelines exist regarding the issue of chemoprophylaxis for infections with STHs or Strongyloides. For pinworm infections, household and other close contacts of an index case should receive a course of presumptive therapy given the high rate of transmission to such persons.
The search for effective vaccines against intestinal nematodes continues, as vaccination offers a simple, cost-effective, single step for control or elimination and is perhaps the most desirable preventative measure. Unfortunately, the lack of good animal models and a poor understanding of how helminths persist in humans in the face of a potent immune response have hindered the development of an effective vaccine. Nevertheless, a hookworm vaccine consisting of the recombinant larval antigen ASP2 is effective in animal models and has shown a protective association in immunoepidemiology studies. The Na-ASP-2 hookworm vaccine is now undergoing clinical development in humans, with Phase I data demonstrating it is safe and antigenic. Phase II trials are ongoing. This vaccine targets the larval forms of hookworms, but not adult worms. Development of a vaccine that will be effective against both the larval and adult stages of hookworms is ongoing. There are no vaccines for the other intestinal nematodes currently in clinical trials.
Primarily, prevention involves better fecal-oral hygiene, provision of clean food and water, good community-wide sanitation, and use of adequate footwear use in endemic areas. As provision of safe water and adequate sanitation is expensive and logistically difficult for many developing countries to implement, the World Health Organization (WHO) advocates treatment with antihelminthic drugs at regular intervals to populations at risk. This is done primarily to reduce individual worm burdens below those that cause significant disease and to decrease the overall community worm burden. Albendazole is safe, inexpensive, and widely available; programs employing this agent (or mebendazole) are, therefore, feasible for most developing countries. Several studies have demonstrated that regular deworming of children (and pregnant/childbearing-age women) can prevent and reverse iron-deficiency anemia, impaired growth, malnutrition, poor school performance, and pregnancy complications.
Although similar large-scale programs targeted specifically for Enterobius or Strongyloides are not widespread, albendazole has activity against both parasites and can likely reduce the burden of disease due to these intestinal nematodes as well. For Strongyloides, albendazole is a second-line therapeutic option (with ivermectin being the preferred agent). In countries co-endemic for lymphatic filariasis and onchocerciasis, which have mass drug administration programs utilizing ivermectin to control these parasites, a salutary effect on Strongyloides is likely.
How do these organisms cause disease?
The pathology stemming from Ascaris infection results from both the host response and the parasite. During larval migration, cells suffer mechanical trauma and lysis due to larval enzymes. Larvae also induce granuloma formation, and Ascaris or hookworm larvae in pulmonary parenchyma cause a hypersensitivity reaction. The pathophysiologic consequences of Ascaris and Trichuris in the gastrointestinal tract stem from the presence of worms in the lumen. Although the severity of symptoms is usually proportional to worm burden, a single worm can (e.g., in the case of Ascaris) obstruct the common bile duct, resulting in severe symptoms.
With Trichuris, heavier infections result in expansion of the ecological niche from the right colon to the entire colon. Production of bloody mucus from the mucosa occurs, with anemia and impaired growth as possible sequelae.
Hookworms, by contrast, exert their primary pathologic effect via blood loss. They attach to the intestinal mucosa by their strong buccal capsules and cutting plates or teeth and secrete anticoagulants and anti-inflammatory factors, allowing continuous blood ingestion. Chronic iron deficiency is particularly detrimental in childhood and may directly impair cognitive and intellectual development.
Human infection with these parasites leads to a predominantly Th2 immune response. It is thought that this shift in immunological response may impact the manifestations of allergic and rheumatologic diseases, as well as the response to infections typically controlled by the Th1 response, such as tuberculosis. There is controversy regarding whether antibodies produced in response to STH infections are protective or merely a marker of past or present infection.
Strongyloides infection is sustained over time in a given host by a small, stable number of intestinal adult worms. Although these die after a finite lifespan, autoinfection ensures the constant production of new worms, perpetuating the cycle even in the absence of re-infection. In patients with chronic strongyloidiasis, autoinfection is normally well controlled by cell-mediated immunity, and the number of adult worms remains low and stable. With immunosuppression, more autoinfective larvae complete the cycle, and the population of parasitic adult worms increases, causing hyperinfection. The large numbers of migrating larvae can disseminate, often associated with polymicrobial sepsis, bronchopneumonia, and meningitis. Untreated, disseminated strongyloidiasis is usually fatal, and even with treatment mortality approaches 25-30%.
Both parasite and host factors affect regulation of this cycle. The population size of S. stercoralis in a host depends, in part, on secreted parasite hormones that regulate autoinfection. When the immune response is impaired, larger numbers of autoinfective parasites can develop, as reported in patients with hematologic malignancies, solid organ and hematopoietic cell transplants, hypogammaglobulinemia, and severe malnutrition. Interestingly, there has been little association between cyclosporine use and hyperinfection syndrome; some evidence suggests cyclosporine may have an antihelminthic effect on S. stercoralis.
Among HTLV-infected patients, there is a strong association with increased susceptibility to infection with Strongyloides, the hyperinfection syndrome, and poor response to treatment. Control of S. stercoralis in vivo is most dependent on the Th2 immune response, but the predominant immune response in HTLV-infected patients shifts from Th2 to Th1. There is some suggestion that S. stercoralis may hasten the development of leukemia among HTLV co-infected patients. In contrast, there have been surprisingly few reports of hyperinfection among S. stercoralis-infected patients with AIDS. Although disseminated strongyloidiasis does occasionally occur in AIDS patients, this disease was removed from the list of AIDS-defining illness by the CDC in 1987.
Corticosteroid use carries a disproportionately high risk for disseminated strongyloidiasis compared to other forms of immunosuppression. Corticosteroids may up-regulate growth of S. stercoralis and allow the parasite to develop preferentially into autoinfective filariform larvae, in addition to suppressing immunity. They may also allow non-reproductive adult worms to regain reproductivity. Patients have developed hyperinfection after only a few days of corticosteroid administration.
WHAT’S THE EVIDENCE for specific management and treatment recommendations?
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- OVERVIEW: What every clinician needs to know
- Parasite name and classification
- What is the best treatment?
- What are the clinical manifestations of infection with these organisms?
- Do other diseases mimic the manifestations of these diseases?
- What laboratory studies should you order and what should you expect to find?
- What imaging studies will be helpful in making or excluding the diagnosis of helminthic infection?
- What complications can be associated with these parasitic infections, and are there additional treatments that can help to alleviate these complications?
- What are the life cycles of these parasites, and how do these life cycles explain infection in humans?
- How do these organisms cause disease?
- WHAT’S THE EVIDENCE for specific management and treatment recommendations?