Chapter 67. Intestinal Parasites

Infections caused by intestinal parasites represent major causes of global morbidity, including malnutrition, diarrhea with dehydration, and anemia. For example, nearly 2 billion people, mostly in resource-poor countries, are infected with one or more of the soil-transmitted nematodes, while cestodes and trematodes are common food-borne infections worldwide. Intestinal protozoa are important causes of diarrhea in travelers, as well as immigrants, refugees, and international adoptees. With the increased global mobility of persons and populations, physicians in the United States are encountering parasitic diseases with increased frequency, requiring familiarity with their clinical features and management. This chapter will focus on the four major classes of intestinal parasite: nematodes, trematodes, cestodes, and protozoa.

(Table 67–1)

Nematodes are unsegemented roundworms belonging to the phylum Nematoda. Many species are found worldwide, but most favor tropical climates. In general, nematodes are cylindrical in shape with tapered ends. They vary greatly in size from up to 40 cm in length (Ascaris lumbricoides) to less than 1 cm (Strongyloides stercoralis, Enterobius vermicularis, and hookworm species). The common finding in this group of worms is the antigenically inert outer layer called the cuticle, which serves as a barrier of protection from host antibodies and digestive enzymes.1,2 Nematodes have separate adult male and female genders, with females typically larger in size.

Ascaris lumbricoides

Epidemiology

A. lumbricoides is the most prevalent of nematode infections, with an estimated 1.4 billion persons infected worldwide. Of those, only a portion have signs of clinical disease, with an estimated 20,000 deaths yearly due to complications of ascariasis.3 Infection occurs in both tropical and temperate climates,2 and in both rural and urban environments,4 typically where adequate moisture and poor sanitation are found. In the United States, the majority of infected individuals are immigrants from endemic areas.3

Pathogenesis

Infection occurs when individuals ingest eggs, often contained in food contaminated with human fecal material, which hatch in the small intestine. The firststage larvae penetrate the intestinal mucosa, enter venous circulation, and travel to the lungs. They then access the alveolar space and migrate up the trachea where they are swallowed, thus returning to the small intestine. During tissue migration, the larvae undergo a series of molts, eventually maturing into adults in the small intestine. Adult females release eggs that are eventually excreted in feces.

Clinical Presentation

A hallmark of Ascaris infection occurs 5–6 days after egg ingestion, just as the larvae travel to the lungs. Termed Loeffler's syndrome, patients often experience wheezing, dyspnea, cough, and fever lasting 10–12 days. Dense pulmonary infiltrates on chest X-ray and moderate eosinophilia (up to 40%) may also be noted. Light to moderate infections may be asymptomatic, although common symptoms include abdominal pain, nausea, anorexia, and diarrhea or constipation. In contrast, those with heavy chronic infections may experience intestinal obstruction, nutritional deficiencies, and cognitive delays.2 Adult worms may also migrate to the bile duct and pancreatic duct, leading to ascending cholangitis, acute pancreatitis, or obstructive jaundice.5

Diagnosis

The diagnosis of A. lumbricoides infection requires identification of characteristic eggs, larvae, or adult worms. When adult worms are producing eggs in the small intestine, light microscopy can be used to identify eggs in the feces. Fertilized eggs are either round or ovoid in shape and measure 60–75 μm in diameter, while unfertilized eggs are elongated and measure up to 90 μm in diameter (Figure 67–1).6 Adult worms may also be passed in stool or exit via the mouth or nares. Adult female worms range in size from 20 to 35 cm in length and 3–6 mm in diameter, while males are slightly smaller.7 The worms are pink in color and tapered at both ends (Figure 67–2). In individuals with Loeffler's syndrome, larvae can occasionally be detected in sputum or bronchoalveolar lavage fluid.

Imaging studies, including abdominal radiographs, ultrasound, and computed tomography (CT) can also establish a diagnosis in heavily infected individuals. On radiographs, large collections of worms can produce a “whirlpool” effect as they contrast with bowel gas.8 Barium is occasionally ingested by the worms, allowing for visualization of the alimentary canal. Ultrasound can detect biliary or pancreatic migration of worms and endoscopic retrograde cholangiopancreatography(ERCP) can aid in removal. CT of the abdomen with oral contrast often reveals cylindrical filling defects within the intestinal lumen. The GI tract of the Ascaris worms can occasionally be seen as a slender thread of contrast within the filling defects.9

Treatment

For A. lumbricoides, the treatments of choice are the benzimidazole anthelminthics, albendazole and mebendazole. Ivermectin and nitazoxanide are also active against A. lumbricoides and can be considered alternative agents (Table 67–5).10 Treatment may trigger active movement of the worms, leading to obstruction or extraintestinal migration.

Strongyloides Species

Epidemiology

Human infection with Strongyloides is usually caused by S. stercoralis, which is endemic to the tropics and subtropics, including parts of the southeastern United States and Appalachia. By contrast, Strongyloides fuelleborni is found in the South Pacific, mainly Papua New Guinea, and parts of Africa. It is estimated that 56 million people are infected with S. stercoralis.11 In the United States, those at highest risk for strongyloidiasis include veterans of World War II and Vietnam, immigrants and refugees from endemic areas, as well as those seropositive for human T-lymphocyte lymphotropic virus type I.12

Pathogenesis

Third-stage free-living larvae penetrate the host skin and gain access to the bloodstream. Once in the venous circulation, their migration is similar to A. lumbricoides, first traveling to the lungs then migrating to the trachea and ultimately into the small intestine. It is here that the larvae become fully mature adults and embed into the intestinal epithelium. The females shed eggs into the gut, which develop into first-stage larvae that are excreted in feces (Figure 67–3).

Strongyloides species are unique among nematodes in that they can complete their entire life cycle outside the host (free living cycle) or multiply within a single host (autoinfective cycle). In autoinfection, larvae develop into the infectious stage within the gut and penetrate the colonic mucosa or perianal skin. Thus, persons can have chronic infections lasting for decades after leaving an endemic area.

Clinical Presentation

Acute infection is characterized by “larva currens,” a serpiginous urticarial rash at the site of skin penetration.13 Migrating larvae in the lung can occasionally induce dyspnea, dry cough, and wheezing. Loeffler's syndrome, characterized by cough, interstitial infiltrates, and eosinophilia, may develop in those with moderate to severe infection, although less commonly than with Ascaris infection. Intestinal symptoms are usually absent in immunocompetent individuals; however, severe, prolonged infections in children can lead to chronic diarrhea, vomiting, weight loss, abdominal distention, malnutrition and lethargy.8 In chronic infection, larva currens is often seen in the perianal area representing autoinfection. In Papua New Guinea, an infantile form of strongyloidiasis (due to S. fuelleborni), called “swollen belly syndrome,” is characterized by abdominal distention, diarrhea, failure to thrive, protein malnutrition, and hypoalbuminemia.14

A feature of S. stercoralis infection is the phenomenon of hyperinfection or disseminated infection. This occurs when a person's cell-mediated immune response is deficient, often due to the administration of immunosuppressives, such as glucocorticoids. Disseminated infection usually involves the bowel (paralytic ileus), central nervous system (CNS) (meningitis, brain abscess), and the lungs (pneumonitis), and may be complicated by secondary bacterial infection and septicemia.15 For this reason, persons from endemic areas about to undergo chemotherapy or long-term steroid therapy are usually screened for evidence of S. stercoralis infection.

Diagnosis

S. stercoralis is unique among intestinal nematodes in that eggs passed by adult female worms develop into larvae within the gut and are excreted in the feces. Although light microscopy may be used to identify larvae, the sensitivity is poor. Multiple samples will increase the detection rate, from 10% with one specimen up to 50% with three.8 Occasionally, the use of a string test or duodenojejunal aspiration can be used to detect larvae.16 With this method, the patient swallows a weighted gelatin capsule attached to a string with the free end taped to the patients’ cheek or neck. After approximately 4 hours, the string is removed and examined for evidence of parasites under light microscopy. In disseminated infection, examination of sputum or lung tissue may also reveal larvae. Peripheral eosinophilia is often found in persons with chronic strongyloidiasis, but may be absent in hyperinfection.17

Serology can aid in the diagnosis of S. stercoralis infection, especially in those with asymptomatic eosinophilia.18,19 However, antibodies persist for years after treatment, thereby limiting the use of serologic tests for distinguishing past from current infection.

Treatment

The drug of choice for strongyloidiasis is ivermectin (Table 67–5). Alternatives include albendazole and thiabendazole.10 In the setting of disseminated infection, it is important to evaluate patients for evidence of concomitant bacterial infection, as well as taper steroids or immunosuppressives as tolerated.20

Hookworm Species (Ancylostoma duodenale and Necator americanus)

Epidemiology

The hookworm species A. duodenale and N. americanus are estimated to infect 740 million people worldwide,5,21 and infection was once endemic in the southeastern United States.22 Other species Ancylostoma ceylanicum and the dog hookworm Ancylostoma caninum less commonly cause intestinal disease. Hookworms primarily infect persons in rural areas and may be associated with farming certain crops (mulberry leaves, sweet potatoes, tea,23 and coffee).

Pathogenesis

The life cycle of hookworms begins when third-stage larvae in the soil contact and penetrate human skin, enter the venous circulation, and are carried to the lungs. After migrating up the trachea, the worms are swallowed and ultimately reach the small intestine. Adult hookworms attach to the intestinal mucosa, lacerating mucosal vessels and ingesting blood (Figure 67–4A and B). The adults mate in the gut, and females release eggs that are excreted in feces (usually appearing within 6–8 weeks after infection).24

Clinical Presentation

Acute infection may cause ground itch, characterized by pruritus and rash, at the site of skin penetration.2 Migration of larvae through the lungs can produce a pneumonitis similar to that seen with A. lumbricoides, although usually less severe. Intestinal disease is usually manifested by nonspecific abdominal pain. Heavy worm burdens, however, may be associated with epigastric pain, nausea, exertional dyspnea, headache, and fatigue. Ingestion of large numbers of A. duodenale larvae may be associated with a condition called Wakana disease, which is characterized by eosinophilia, nausea, vomiting, and dyspnea.24

Chronic infection may lead to anemia, malnutrition, and growth delay, and can be associated with cognitive delay. It is estimated that each adult hookworm can feed on up to 0.2 mL of blood per day, resulting in iron-deficiency anemia and hypoproteinemia.4 A form of neonatal disease, similar to that caused by S. fuelleborni, is characterized by melena, abdominal distention, hypotension, and severe anemia.25,26

Diagnosis

Identification of eggs in fecal samples is the mainstay of diagnosis. The eggs are 50–75 μm in length by 35–45 μm in width, with a thin shell and oval or ellipsoid shape (Figure 67–5A and B).6 Heavily infected persons also have iron-deficiency anemia, hypoalbuminemia, and mild eosinophilia.

Treatment

Hookworm infection is generally treated with albendazole or mebendazole, with pyrantel pamoate a suitable alternative (Table 67–5). Nitazoxanide may also have activity,27 although data are limited. Eradication programs in endemic countries have relied on targeted chemotherapy of children, which results in short-term improvements in blood hemoglobin levels and nutritional status.24 However, high rates of reinfection and potential emergence of anthelminthic resistance may limit the long-term benefit of current control measures.26

Enterobius vermicularis

Epidemiology

E. vermicularis (pinworm) is the most common nematode infection in developed countries, mainly affecting preschool children. Infection occurs through fecal–oral contamination, ingestion of fomites (airborne eggs), and/or retroinfection.28

Pathogenesis

Once pinworms eggs are ingested, they hatch and release larvae in the small intestine. Here they undergo several molts until they mature into adults and eventually reach the colon (usually a 5-week process). Female adult pinworms migrate out of the intestine at night and deposit eggs on the perianal skin. Each female can produce as many as 11,000 eggs per day,29 which become infectious within hours.

Clinical Presentation

Pruritus ani, caused by the inflammatory response directed at eggs deposited on the perianal skin, may lead to secondary cellulitis and subcutaneous abscess formation.30 Aberrant migration of the adult worms may result in endometritis, salpingitis, and rarely appendicitis.28,31

Diagnosis

Since eggs are deposited in the perianal area instead of in the feces, they are not detected using standard microscopy for ova and parasites. For this reason, it is recommended that a piece of clear adhesive tape be looped over a tongue depressor so that the adhesive surface is on the outside. The tape is then pressed against the perianal skin in several places and attached to a glass slide, which is examined under light microscopy for the presence of eggs. The optimal time for this test is early morning before bathing. Pinworm eggs are ovoid and measure 50–60 μm in length by 20–30 μm in width (Figure 67–6).6 Adult worms may reach 1 cm in length and are distinguished by bilateral cuticular ridges termed alae.2

Treatment

E. vermicularis infection is treated with mebendazole, albendazole, or pyrantel pamoate (Table 67–5).10 A second treatment after 2 weeks is recommended to eradicate developing larvae, as these anthelminthics are not ovicidal. Recurrent disease is common, most often due to reinfection from an infected close contact.

Trichuris trichiura

Epidemiology

Also known as the whipworm, infections with T. trichiura occur in most parts of the tropics, similar to A. lumbricoides and hookworm. The estimated number of people infected worldwide is 795 million.21

Pathogenesis

The life cycle is similar to that of E. vermicularis in that infectious eggs are swallowed and hatch in the small intestine. Larvae undergo several molts until they mature into adults and eventually reside in the colon. The adult whipworms, which can reach 5 cm in length, embed into the colonic mucosa where the males and females mate. Here the females excrete up to 20,000 eggs per day in the stool, taking at least 2–3 months from infection before egg production starts.2 Unlike E. vermicularis eggs, which become infectious soon after deposition, the eggs of T. trichiura only become infectious after 15–30 days.6

Clinical Presentation

Light infections are usually asymptomatic. Heavy infections can lead to a severe inflammatory colitis known as Trichuris dysentery,32 characterized by melena and mucus in the stool. Mucosal edema also may develop, leading to rectal prolapse (Figure 67–7). Chronic infections can lead to a colitis that mimics inflammatory bowel disease and may be associated with growth delay and cognitive deficits.33

Diagnosis

Light microscopy is most commonly used to detect characteristic eggs in the feces. The eggs are oval in shape (sometimes referred to as “barrel shaped”), and have a three-layer eggshell as well as transparent bipolar mucoid plugs (Figure 67–8). They usually measure 50–54 × 22–23 μm.6

Treatment

The drug of choice for T. trichiura infection is mebendazole (500 mg in a single dose for light infections; 100 mg bid × 3 days for heavy infections). Alternative drugs are albendazole and ivermectin (Table 67–5). Of note, T. trichiura is resistant to pyrantel pamoate.10

Education, targeted chemotherapy, and improved sanitation efforts (building of proper latrines) helped to reduce the burden of intestinal nematode infections in the United States.22 In resource poor countries, mass deworming may reduce nutritional deficiencies and growth stunting, although this strategy confers only short-term benefit due to high rates of reinfection. For travelers to endemic areas, education about transmission is important. Wearing proper footwear and proper cooking of food and filtering (or boiling) of drinking water may reduce the risk of transmission. Although currently in development, no vaccines are yet available for human soil-transmitted nematode infections.

(Table 67–2)

Trematodes, also known as flukes, belong to the phylum Platyhelminthes and are characteristically flat and leaf-like. An estimated 50 million people are infected with intestinal flukes in North Africa, the Middle East, and East and Southeast Asia.34 Many trematodes are hermaphrodites, with both male and female reproductive organs in a single worm. Each trematode has two suckers, an anterior oral sucker that connects to the alimentary canal, and a posterior ventral sucker that attaches the worm to the host (Figure 67–9).2 These worms have no true intestine, as the alimentary canal ends in a blind pouch. Liquid waste is therefore expelled through specialized excretory cells known as flame cells, and insoluble waste must be regurgitated through the apical sucker.4 Unique to trematodes is the requirement of the snail as an intermediate host. The major intestinal flukes are Fasciolopsis buski, Heterophyes heterophyes, and Metagonimus yokogawai.

Fasciolopsis buski

Epidemiology

Found predominantly in the Far East, F. buski is endemic in the Yangtze basin provinces of China and parts of Southeast Asia and India where both pigs and water plants are farmed.2

Pathogenesis

When human feces containing eggs contaminate a body of water, the eggs embryonate and hatch, releasing larvae called miracidium. The miracidium infect specific freshwater snails and develop into cercariae, which are shed and encyst on plants. Here, the larvae develop into metacercaria. When raw or undercooked plants (watercress, bamboo shoots, and water chestnuts) containing these metacercaria are consumed by humans, the larvae migrate to the small intestine and mature into adult flukes. The larvae take approximately four months to fully mature at which time they can produce up to 28,000 eggs per fluke per day.2

Clinical Presentation

Clinical symptoms result from the attachment of the flukes to the intestinal mucosa causing inflammation, ulceration, and microabscesses. Heavy worm burdens (>500 adult worms) can produce significant symptoms, such as diarrhea, constipation, abdominal pains, nausea, and vomiting. Heavy infections with F. buski can also lead to intestinal obstruction or a protein-losing enteropathy.34

Diagnosis

Recovery of characteristic eggs in the stool is the key to diagnosis. The eggs may be best demonstrated after concentrating stool, especially in the case of light infections. F. buski has larger eggs than the other intestinal flukes and measures 130–140 by 80–85 μm in size (Figure 67–10A).2 The eggs are operculated and are unembryonated when deposited. The adult flukes, if recovered, reach up to 7.5 cm in length and 2.5 cm in width, and are easily recognized when compared to other Fasciola species because of the absence of a cephalic cone (Figure 67–10B).35

Treatment

The preferred treatment for F. buski is praziquantel (Table 67–5).10

Heterophyes heterophyes and Metagonimus yokogawai

Epidemiology

H. heterophyes can be found in most parts of Asia, as well as in North Africa and the Middle East. M. yokogawai represents the most common intestinal fluke in the Far East, but has also been found in Spain, Israel, and Serbia.2

Pathogenesis

The life cycles of these species are very similar to that of F. buski. When humans consume raw or undercooked fish containing metacercaria, the larvae migrate to the small intestine and mature into adult worms. The types of fish that transmit disease are usually found in either brackish or fresh water.34

Clinical Presentation

The smaller flukes (H. heterophyes and M. yokogawai) can penetrate the intestinal mucosa, eliciting a granulomatous response. They may occasionally migrate to ectopic sites, such as the heart and brain via the bloodstream and lymphatics. Symptoms include abdominal pain, intermittent diarrhea, anorexia, and nausea.34

Diagnosis

The eggs of H. heterophyes and M. yokogawai are much smaller in size than F. buski. Treatment may result in expulsion of the adult worms, allowing for a definitive diagnosis. The adult worms of H. heterophyes and M. yokogawai are 1–1.7 mm in length by 0.3–0.4 mm in width and 1–2.5 mm in length by 0.4–0.75 mm in width, respectively (Figure 67–11A and B).6

Treatment

Similar to F. buski, the preferred treatment is Praziquantel (Table 67–5).10

Properly cooking plants (such as bamboo shoots and watercress) may help to prevent infection. The practice of eating raw fish in endemic areas should also be discouraged. Ultimately, improving sanitary conditions in endemic areas to prevent fecal contamination in water sources where plants and fish live is the most effective long-term control strategy.

(Table 67–3)

Cestodes, belonging to the phylum Platyhelminthes, are also commonly known as tapeworms because of their flat, ribbon-shaped appearance. The tapeworm morphology consists of a scolex, which attaches to the host's intestinal mucosa via suckers or sucking grooves, and/or hooks. Just posterior to the scolex is the neck, which gives rise to the growth of proglottids. The tapeworm grows distally in a process known as strobilation; thus the further away from the neck region, the proglottids become successfully more mature and then gravid. Once they fill with eggs, the proglottid becomes detached and is excreted in the stool. Similar to flukes, tapeworms are hermaphroditic, as each proglottid contains both ovaries and testes. There are four major groups of cestodes, but only those in the orders Cyclophylidea (Taenia saginata, Taenia solium, Hymenolepis nana) and Pseudophylidea (Diphylobothrium latum) are important intestinal pathogens.

Taenia saginata and Taenia solium

Epidemiology

T. saginata, the beef tapeworm, is endemic to Europe, Africa and South America because of the customary practice of consuming undercooked beef. T. solium, related to pork consumption, is common in Mexico, Central and South America, parts of Africa and Southeast Asia.2 Infection with the larval stages of T. solium, called cysticercosis, is a major cause of seizures in resource-poor countries.

Pathogenesis

The life cycles of T. saginata and T. solium are quite similar. When either cattle or pigs consume feed contaminated with human feces containing Taenia eggs, the eggs hatch in the intestine and travel via the bloodstream and lymphatics to somatic tissues. Here, they develop into the larval forms (cysticerci). When humans ingest undercooked beef or pork containing cysticerci, the larvae are released from the cyst and attach to the intestinal epithelium via the scolex. Here the tapeworms grow distally, reaching lengths of 2–4 m for T. solium (800–900 proglottids) and 5–25 m for T. saginata (1000–2000 proglottids).8 Maturation into the adult form takes 6–8 weeks for T. solium and 10–12 weeks for T. saginata, at which time proglottids may be shed.36 If untreated, tapeworms can survive for up to 25 years for T. solium, and 10 years for T. saginata.8

If humans ingest T. solium eggs directly via fecal–oral contamination, the eggs hatch and invade the circulatory system and disseminate to somatic tissues. Neurocysticercosis is the term that refers to CNS invasion by the larvae.

Clinical Presentation

Intestinal taeniasis is usually asymptomatic. Occasionally infected individuals experience vague symptoms, including abdominal pain, nausea, diarrhea, and appetite changes. Many become aware of infection only after the passage of tapeworm segments in the stool.36

Diagnosis

Demonstration of eggs or gravid proglottid segments in the feces is necessary for the diagnosis of intestinal taeniasis. For T. solium and T. saginata, the eggs are morphologically indistinguishable, described as brown and spherical, measuring 31–43 μm in diameter (Figure 67–12). 6 The gravid proglottid segments allow for distinction between species. T. solium proglottids are usually expelled passively in chains of five or six segments while that of T. saginata are expelled as single proglottids and may even crawl out of the anus. The uterine branches and testicular follicles in each segment also differ; T. solium have fewer uterine branches (5–10) and testicular follicles (150–200) while that of T. saginata have 15–30 branches and 300–400 testicular follicles (Figure 67–13A and B).8

Occasionally, the scolex will be passed in the stool and will allow for differentiation between species. The scolex of T. solium has a rostellum with a double row of hooklets (22–32) and four suckers. In contrast, T. saginata has an unarmed rostellum (the absence of hooklets) (Figure 67–14A and B).37

Fecal coproantigen detection assays have been developed to detect Taenia-specific antigens in human specimens.38 This is a sensitive and specific test, although not widely available. Serology is useful for the diagnosis of T. solium infection in the setting of cysticercosis, especially neurocysticercosis, although its role in diagnosing intestinal disease is less certain.

Treatment

The mainstay of treatment for intestinal taeniasis is praziquantel (Table 67–5).10 One to three months after therapy, patients should be examined for evidence of eggs in the stool to document cure.

Hymenolepis nana

Epidemiology

H. nana, also known as the dwarf tapeworm, is the most common tapeworm to infect humans, and has a global distribution.39

Pathogenesis

H. nana does not require an intermediate host. Rather, humans ingest eggs (via fecal–oral contamination) that hatch in the small intestine releasing a larval form called the oncosphere. This penetrates the intestinal mucosa and matures into cysticercoid larva in the lymphatics of the intestinal villi. The cysticercoid then migrates back into the intestinal lumen, where it attaches via its scolex and grows distally as it matures, eventually achieving lengths of 2–4 cm.36 It takes 3–4 weeks from the start of infection before eggs appear in the stool.39 This entire life cycle can be completed in a single host, unlike the other intestinal tapeworms.

Clinical Presentation

While most cases are asymptomatic, heavy infection with H. nana (>1000 worms) can cause intestinal inflammation with diarrhea, abdominal pain, anorexia, and pruritus ani.36,39

Diagnosis

As noted above, H. nana adult worms are much smaller in size than other tapeworms, and contain up to 200 proglottids.2 The scolex has four suckers and hooklets. The diagnosis is usually made by demonstration of eggs in feces. The eggs measure 30–55 μm in diameter and can be spherical or oval shaped with a two-layered shell (Figure 67–15).6

Treatment

The treatment of choice is praziquantel (Table 67–5). One to three months after therapy, patients should be rechecked for evidence of eggs in the stool to document cure.10

Similar to E. vermicularis (pinworms), when children are infected with H. nana, many experts recommend screening and treating family members, since person-to-person spread has been documented.

Diphylobothrium latum

Epidemiology

D. latum, the fish tapeworm, is endemic in Japan and Northern Europe where consumption of raw fish is common.8 An estimated 20 million people are infected worldwide.2 Infection has been reported after the consumption of sushi40 and in the United States after sampling raw gefilte fish.8

Pathogenesis

The life cycle of D. latum requires two intermediate hosts prior to human infection. When eggs from human feces contaminate water, the eggs hatch and form coracidium (a larval form). When ingested by a small freshwater crustacean, termed a copepod, the next larval stage, called the procercoid, develops. If a fish ingests the infected copepod, the procercoid invades the stomach wall of the fish and disseminates to the muscle tissue, where it matures to a plerocercoid larvae. When humans ingest raw or undercooked infected fish, the plerocercoid larvae matures into adult form and can grow to 15 m in length39 with 3000–4000 proglottid segments (Figure 67–17A and B).8

Clinical Presentation

Most infected individuals are asymptomatic, however, some may experience nonspecific symptoms such as abdominal pain, weight loss, vomiting, and anorexia. Chronic infection can lead to macrocytic anemia from vitamin B12 deficiency.2 Although up to 40% of patients may have subclinical vitamin B12 deficiency, only 2% develop anemia.8

Diagnosis

Diagnosis of D. latum requires the detection of eggs or proglottid segments in feces, which usually appear one month after consumption of infected fish. The eggs are released from a uterine pore and measure 55 by 60 μm and have both an operculum and a small knob (Figure 67–16).8 If passed in the stool, the scolex of D. latum has a spoon shape and contains bothria (grooves) that allow attachment to the intestinal wall. Unlike the Taenia species, there are no suckers or hooklets.8

Treatment

The recommended treatment is praziquantel (Table 67–5). As with other tapeworms, a repeat stool specimen should be examined 1 to 3 months after treatment to document cure.

Prevention of tapeworm infections requires education and safe eating practices. Thoroughly cooking beef, pork and fish will kill cysticerci and plerocercoids, thereby preventing infection. Prevention of H. nana infection requires adequate sanitation.

(Table 67–4)

Intestinal protozoa are unicellular organisms spread via ingestion of contaminated food and water. The most common intestinal protozoa are Giardia lamblia and Entamoeba histolytica (known as amebiasis), both of which cause disease worldwide. Other species cause significant disease primarily in those who are immunocompromised, including Cryptosporidium parvum, Cyclospora cayetanensis, and Isospora belli. The pathogenic potential of two other protozoa, Blastocystis hominis and Dientamoeba fragilis, is controversial.

Giardia lamblia

Epidemiology

In the United States, G. lamblia remains a common cause of waterborne diarrhea, with numerous outbreaks recorded. The prevalence in developed countries is estimated at 2–5% while that in developing countries may be as high as 20–30%.41 Those at highest risk appear to be infants and young children (especially those in day care centers, where person-to-person transmission can occur), immunocompromised individuals (especially those with common variable immunodeficiency and X-linked agammaglobulinemia), and travelers to high prevalence areas (accounting for 5% of traveler's diarrhea).42 Contaminated water serves as the most common source of human infection in the United States, with waterborne outbreaks occurring in mountainous areas as well as swimming pools after a fecal accident. There is also reason to believe that mammals (both wild and domestic) serve as reservoirs for this organism. Transmission may also occur through sexual activity as a result of oroanal contact.41

Pathogenesis

After ingestion of as few as 10–100 Giardia cysts, the organisms excyst in the small intestine and release two trophozoites, which embed within the crypts. Here the trophozoites multiply by binary fission and encyst. After being excreted in feces, cysts may contaminate water sources and infect animals, which serve as a reservoir for human infection.41Giardia cysts survive for months in cool, moist conditions, and are relatively resistant to chlorination.42,43

Clinical Presentation

Some individuals who harbor G. lamblia may be asymptomatic, serving as a reservoir for infection of others. Symptoms of infection include acute diarrhea, especially in travelers, who may also experience weight loss, abdominal discomfort, and flatulence beginning within 7 days of cyst ingestion. Chronic giardiasis occurs in 30–50% of infected persons, and is characterized by steatorrhea, weight loss, secondary lactase deficiency, Vitamin A and B12 deficiency, and even hypoalbuminemia.41 In young children with chronic infection, nutritional deficiencies can lead to delays in growth and development.

Diagnosis

Stool examination for trophozoites and cysts should be performed using light microscopy. Trophozoites are more commonly found in watery stools, and cysts are more commonly found in formed specimens.6 At least three specimens should be submitted and occasionally the stool must be concentrated to confirm the diagnosis. The cysts are round or oval and measure 8–12 μm in length (Figure 67–18A). The trophozoites are pear-shaped and measure 9–20 μm in length with two large nuclei and one large central karyosome (Figure 67–18B and C).6

Currently, fecal antigen detection and serology are both commercially available to help aid in diagnosis.43 Fecal antigen testing has reported sensitivities of 87–100%.41 Serology, on the other hand, is not helpful in distinguishing past from present infection.

Treatment

The drugs of choice are metronidazole, nitazoxanide, and tinidazole (Table 67–5). Alternatives include paromomycin and furazolidone.10

Entamoeba histolytica

Epidemiology

The prevalence of E. histolytica is highest in developing countries, where water and food are subject to fecal contamination. In the United States, the majority of disease is found among immigrants from Mexico, Central America, South American, Asia, and the Pacific Islands.44 Travelers to endemic areas are also at risk.

Pathogenesis

The life cycle of E. histolytica is similar to that of G. lamblia. Humans, thought to be the primary reservoir, ingest cysts in contaminated food or water. In the small intestine, they excyst to form trophozoites, which are highly motile and reproduce via binary fission. Here the trophozoites may lead to the development of flask-shaped ulcers and mucosal thickening mimicking inflammatory bowel disease. To complete the life cycle, the trophozoites encyst and are passed in the feces.

Clinical Presentation

Many infected individuals are asymptomatic. Some develop amebic colitis, characterized by bloody diarrhea, abdominal pain, and tenderness. Others, especially those who are immunocompromised,45 pregnant, or receiving corticosteroids, may develop fulminant colitis, with fever, leukocytosis, profuse bloody diarrhea, widespread abdominal pain, and peritoneal signs. Many of these individuals develop intestinal perforation, with an associated mortality rate of up to 40%.44 Amebomas, which represent annular granulation tissue in the colon that can mimic carcinoma,46 may cause obstructive symptoms.

A common extraintestinal manifestation is amebic liver abscess, which occurs in the absence of gastrointestinal symptoms and is characterized by fever, right upper quadrant pain, and tenderness.44

Diagnosis

Light microscopy, perhaps the most commonly used method of diagnosing amebiasis, does not differentiate E. histolytica from other commensal organisms, such as Entamoeba dispar. The trophozoites are 15–20 μm in size (range of 10–60 μm) and have a single nucleus with granular cytoplasm (Figure 67–19A). The cysts usually measure 12–15 μm and have four nuclei (Figure 67–19B).6 Commercially available enzyme-linked immunosorbent assay (ELISA) can identify specific E. histolytica antigens in the stool.47,48 These are more sensitive than microscopy and can distinguish E. histolytica from E. dispar.

In the setting of liver abscess, serology is highly sensitive (>94%) and specific (>95%).44 Currently, the Centers for Disease Control (CDC) offers E. histolytica antibody detection via enzyme immunoassay (EIA).

Treatment

To limit the spread of disease, even asymptomatic carriers should be treated. The drugs of choice vary depending on the severity and location of disease (Table 67–5). Individuals with symptomatic disease should be treated with a luminal agent, such as paromomycin or iodoquinol, after primary treatment is given to eradicate colonization. Amebic liver abscess can usually be treated with metronidazole, although surgical intervention is occasionally necessary.44

Cryptosporidium parvum

Epidemiology

C. parvum is prevalent worldwide, with an estimated 20% of children in the United States seropositive. In developing countries, studies reveal up to a 90% seroprevalence in young children.49 Higher infection rates are seen in immunocompromised individuals, particularly in persons with acquired immunodeficiency syndrome (AIDS).50 Some reasons for its widespread prevalence include chlorine resistance, a small infectious dose, and possible zoonotic transmission. In the United States, a 1993 outbreak of C. parvum in Wisconsin was traced to contamination of the public water source.51

Pathogenesis

Infection with C. parvum begins with the ingestion of oocysts. Once in the GI tract, the oocysts excyst and release sporozoites, which attach to intestinal epithelial cells. Sporozoites undergo asexual reproduction and release merozoites, which either infect new epithelial cells or mature into gametocytes. Gametocytes undergo sexual reproduction, and when fertilized, form thin and thick walled cysts. The thin walled cysts autoinfect the host, while thick walled cysts are released in the feces.50

Clinical Presentation

Persons with C. parvum infection range from being asymptomatic to having profuse watery diarrhea with extraintestinal infection. In immunocompetent persons, the incubation period of 7–10 days is followed by abdominal pain and cramping, watery diarrhea with mucous (without hematochezia), weight loss, and occasionally fever and vomiting.50 Children in developing countries may develop chronic infection, leading to malnutrition and growth delay.

In persons with AIDS or other immunocompromised conditions, infection may be more severe. Those with low CD4 counts (<50/mm3) may have profuse (up to 2 L per day) and watery diarrhea. These patients are less likely to spontaneously clear the infection, and may have extraintestinal disease, such as biliary infection.50

Diagnosis

The diagnosis of cryptosporidiosis is usually made by demonstration of oocysts in stool using light microscopy and modified acid-fast staining. Of note, clinical laboratories do not routinely perform this test, and one must therefore request examination specifically for C. parvum.49 The oocysts are 4–6 μm in size and round with no visible nuclei (Figure 67–20).52 Direct fluorescent antibody tests, specific fecal antigen tests, and polymerase chain reaction (PCR) techniques with high sensitivities and specificities are also available.49,50 Serology is available, but because of the widespread prevalence of antibodies to C. parvum, a positive result is not diagnostic of current infection.

Treatment

In immunocompetent persons, cryptosporidiosis is usually self-limited, and treatment is not required. Malnourished children or adults with prolonged shedding may benefit from therapy with nitazoxanide (Table 67–5).53,54 For persons with AIDS, therapy with nitazoxanide may also confer some benefit, but recent evidence shows that highly active antiretroviral therapy (HAART) therapy is most effective at decreasing the duration of illness.49

Cyclospora cayetanensis and Isospora belli

Epidemiology

Humans are the only known reservoirs for C. cayetanensis, unlike I. belli, which can infect both humans and animals. These spore-forming protozoa typically cause disease in tropical and subtropical regions.55C. cayetanensis can also be found in developed countries, mainly in persons who have traveled to an endemic area or by consumption of contaminated food from an endemic area. In human immunodeficiency virus (HIV)-infected patients with CD4 T-cell counts less than 200/mm3, persistent infections are being increasingly identified.56

In the United States, several large outbreaks of C. cayetanensis have been reported related to consumption of contaminated raspberries imported from Guatemala, as well as basil grown in the United States and Mexico.15 Waterborne transmission has also been documented.57,58

Pathogenesis

Oocysts released in the feces of persons infected with either C. cayetanensis or I. belli are unsporulated and require several weeks to become infectious. Humans ingest the infectious oocysts, which enter the small intestine epithelium and replicate intracellularly. Newly formed oocysts rupture the epithelial cells and are shed in human feces to complete the transmission cycle.56

Clinical Presentation

In immunocompetent individuals, infection with either Cyclospora or Isospora can lead to abdominal cramps and watery, nonbloody diarrhea lasting for up to 6 weeks. Accompanying symptoms include nausea, vomiting, muscle aches, fatigue, and low-grade fever. In highly endemic areas, asymptomatic as well as relapsing–remitting infections occur.55 In immunocompromised individuals, including those with HIV infection, the clinical course can be more severe and prolonged.

Diagnosis

The diagnosis is best accomplished by examination of the stool by light microscopy. Often more than one sample is needed (preferably three), and if the sample cannot be examined promptly, the stool should be refrigerated or placed in a preservative. Several diagnostic techniques are available, including wet mounts using differential interference contrast or UV fluorescence microscopy. Special stains, such as modified acid-fast and safranin, may also be used. C. cayetanensis is round and measures 8–10 μm in diameter (Figure 67–21), while I. belli cysts are larger and ellipsoidal in shape, measuring 25–30 μm (Figure 67–22).6

Treatment

The treatment of choice for both infections is trimethoprim/sulfamethoxazole. Refer to the Table 67–5 for details.

Blastocystis hominis and Dientamoeba fragilis

Epidemiology

The degree to which these two protozoa cause intestinal disease remains controversial. Both share a worldwide distribution and occur in all ages. Prevalence studies have shown that these organisms are common in both developed and resource-poor countries, and in symptomatic as well as healthy asymptomatic individuals. Up to 15% of stool samples in the United States are positive for B. hominis compared to reported rates of 30–50% in developing countries.59 Surveillance for D. fragilis suggests that it occurs less commonly in the United States than B. hominis.60

Pathogenesis

The life cycles and mechanisms of pathogenesis for these two protozoa remain poorly understood. In the case of B. hominis, four forms of the protozoa have been described: vacuolar, granular, ameboid, and cystic. However, the phenotype most involved in transmission has not yet been defined. For D. fragilis, a cyst form has not been identified, and so it is unclear how this pathogen survives in the environment, as well as the acidity of the stomach if the route of transmission is fecal–oral.

Clinical Presentation

Much of the known spectrum of illness associated with carriage of these organisms comes from case reports, rather than well-controlled clinical studies. Symptoms of nausea, anorexia, abdominal pain, vomiting, fatigue, and watery diarrhea have been reported, although many individuals who harbor these organisms are asymptomatic.52,59,60 One difficulty in defining the pathogenicity of B. hominis and D. fragilis is that excretion of these organisms often coincides with excretion of other established intestinal pathogens.

Diagnosis

B. hominis usually measures between 5 and 40 μm and lacks a cell wall. A stained smear of unconcentrated stool (usually with hematoxylin or trichrome stain) is the preferred method of diagnosis.59 The size of D. fragilis also varies widely.60 They have a rounded appearance on wet mount and as the name suggests, they are binucleate and rapidly degenerate after excretion in the feces. Similar to B. hominis, permanently stained smears of stool are the preferred method of diagnosis.

Treatment

There are no consensus guidelines for treatment of Blastocystis or Dientamoeba. In the absence of symptoms, treatment is not warranted. However, if a patient has symptoms and no other pathogens have been identified, treatment with antiparasitic agents (Table 67–5) may be considered. Case reports and small placebo-controlled trials suggest that treatment may improve symptoms in some individuals.59–61

Similar to other intestinal parasites, precautions to prevent fecal–oral contamination will potentially reduce transmission of intestinal protozoa. For travelers, bottled, filtered, or boiled water should be used for drinking and brushing teeth. Consumption of ice and raw fruits and vegetables should be avoided.