135 - 239 Intestinal Nematode Infections

239 Intestinal Nematode Infections

fish or poultry. Raw fish dishes, such as som fak in Thailand and sashimi in Japan, account for many cases of human gnathostomiasis. Some cases in Thailand result from the local practice of applying frog or snake flesh as a poultice.

Pathogenesis and Clinical Features  Clinical symptoms are due to the aberrant migration of a single larva into cutaneous, visceral, neural, or ocular tissues. After invasion, larval migration may cause local inflammation, with pain, cough, or hematuria accompanied by fever and eosinophilia. Painful, itchy, migratory swellings may develop in the skin, particularly in the distal extremities or periorbital area. Cutaneous swellings usually last ~1 week but often recur intermit­ tently over many years. Larval invasion of the eye can provoke a sightthreatening inflammatory response. Invasion of the CNS results in eosinophilic meningitis with myeloencephalitis, a serious complication due to ascending larval migration along a large nerve tract. Patients characteristically present with agonizing radicular pain and paresthe­ sias in the trunk or a limb, which are followed shortly by paraplegia. Cerebral involvement, with focal hemorrhages and tissue destruction, is often fatal. Diagnosis and Treatment  Cutaneous migratory swellings with marked peripheral eosinophilia, supported by an appropriate geo­ graphic and dietary history, generally constitute an adequate basis for a clinical diagnosis of gnathostomiasis. However, patients may present with ocular or cerebrospinal involvement without anteced­ ent cutaneous swellings. In the latter case, eosinophilic pleocytosis is demonstrable (usually along with hemorrhagic or xanthochromic CSF), but worms are almost never recovered from CSF. Computed tomography or magnetic resonance imaging of the brain during neu­ ronal gnathostomiasis often demonstrates cerebral hemorrhage from the destructive migration of the parasite. Surgical removal of the parasite from subcutaneous or ocular tissue, though rarely feasible, is both diagnostic and therapeutic. Albendazole or ivermectin may be helpful, especially for cutaneous gnathostomiasis (Table 238-1). At present, cerebrospinal involvement is managed with supportive measures and generally with a course of glucocorticoids; the role of albendazole or ivermectin is uncertain and could be detrimental. Gnathostomiasis can be prevented by adequate cooking of fish and poultry in endemic areas. PART 5 Infectious Diseases ■ ■FURTHER READING Auer H, Walochnik J: Toxocariasis and the clinical spectrum. Adv Parasitol 109:111, 2020. Centers for Disease Control and Prevention: Surveillance for trichinellosis—United States, 2015, Annual Summary. Atlanta, GA: U.S. Department of Health and Human Services, CDC, 2017. Clinical Subcommittee of the Hawaii Governor’s Joint Task Force on Rat Lungworm Disease. Preliminary guidelines for the diagnosis and treatment of human neuroangiostrongyli­ asis (rat lungworm disease) in Hawaii. https://health.hawaii.gov/docd/ files/2018/08/RLWD_Preliminary_Clinical_Guidelines_FINAL_082918. pdf.  Accessed December 1, 2023. Diaz JH et al: The disease ecology, epidemiology, clinical manifestations, and management of trichinellosis linked to consumption of wild animal meat. Wilderness Environ Med 31:235, 2020. Lupi O et al: Mucocutaneous manifestations of helminth infections. Nematodes. J Am Acad Dermatol 73:929, 2015. Martins YC et al: Central nervous system manifestations of Angiostrongylus cantonensis infection. Acta Trop 141:46, 2015. Rostami A et al: Meat sources of infection for outbreaks of human trichinellosis. Food Microbiol 64:65, 2017. Sitcar AD et al: Raccoon roundworm infection associated with cen­ tral nervous system disease and ocular disease—six states, 2013–2015. Morbid Mortal Wkly Rep 65:930, 2016.

David J. Diemert, Thomas B. Nutman

Intestinal Nematode

Infections More than one billion individuals worldwide are infected with one or more species of intestinal nematode. Table 239-1 summarizes biologic and common clinical features of infections due to the major intestinal parasitic nematodes. These parasites are most common in regions with inadequate sanitation and disposal of fecal waste, particularly in resource-limited countries in the tropics and subtropics, although they have also been seen with increasing frequency among immigrants and refugees to developed countries. Although intestinal nematode infec­ tions are not usually fatal, they contribute to malnutrition, impaired physical and cognitive development, and diminished work capacity. It is interesting that these helminth infections may protect some indi­ viduals from allergic diseases. Humans may on occasion be infected with nematode parasites that ordinarily infect animals; these zoonotic infections produce diseases such as trichostrongyliasis, anisakiasis, capillariasis, and abdominal angiostrongyliasis. Intestinal nematodes are roundworms that range in length from 1 mm to many centimeters when mature (Table 239-1). Their life cycles are complex and highly varied; some species, including Strongyloides stercoralis and Enterobius vermicularis, can be transmitted directly from person to person, while others, such as Ascaris lumbricoides, Trichuris trichiura, and the hookworms, require a soil phase for devel­ opment. Because most helminth parasites cannot fully complete their life cycle within the same human host, heavy burdens of adult worms require repeated exposure to the parasite in its infectious stage, whether larva or egg. Hence, clinical disease, as opposed to asymptomatic (or subclinical) infection, generally develops only with repeated exposure and is typically related to infection intensity. In children with marginal nutritional status, intestinal helminth infections may impair growth and development. Eosinophilia and elevated serum IgE antibody levels are features of many helminth infections, the latter particularly when the helminth life cycle involves tissue migration such as A. lumbricoides, S. stercoralis, or the hookworms. Significant protective immunity to intestinal nematodes appears not to develop in humans. ■ ■ASCARIASIS A. lumbricoides is the largest intestinal nematode parasite of humans, reaching up to 40 cm in length. Most infected individuals have low worm burdens and are asymptomatic. Clinical disease arises from larval migra­ tion in the lungs or the effects of adult worms in the intestines. Life Cycle  Adult worms live in the lumen of the small intestine. Mature female Ascaris worms are extraordinarily fecund, each pro­ ducing over 200,000 eggs a day that are expelled within feces. Ascarid eggs, which are remarkably resistant to environmental stresses, become infective after several weeks of maturation in warm, moist soil and can remain infective for years. After infective eggs are swallowed, gastric acid dissolves their protective outer layer, releasing larvae into the intestine that invade the mucosa, migrate through the circulation to the lungs, penetrate into the alveoli, ascend the bronchial tree, and return— through swallowing—to the small intestine, where they develop into adult worms. The time between initial infection and egg detection in the feces is typically between 2 and 3 months. Adult worms live for 1–2 years. Epidemiology  Ascaris is widely distributed in tropical and sub­ tropical regions as well as in other humid areas in more temperate regions of the world. Transmission typically occurs through fecally contaminated soil and is due either to inadequate treatment of sewage or to the use of human feces as fertilizer. With their propensity for poorer oral hygiene, younger children are most often affected. Infec­ tion outside endemic areas, though uncommon, can occur when eggs on transported produce are ingested.

TABLE 239-1  Major Human Intestinal Parasitic Nematodes NECATOR AMERICANUS, ANCYLOSTOMA DUODENALE, ANCYLOSTOMA CEYLANICUM (HOOKWORM) ASCARIS LUMBRICOIDES (ROUNDWORM) FEATURE Global prevalence in humans (millions)

Endemic areas Hot, humid regions Hot, humid regions Hot and warm, humid regions Hot, humid regions Worldwide Infective stage Egg Filariform larva Filariform larva Egg Egg Route of infection Oral Percutaneous Percutaneous or autoinfective Gastrointestinal location of worms Small intestine Jejunal mucosa Small intestinal, mucosa Cecum, colonic mucosa Adult worm size 15–40 cm 7–13 mm 1–2 mm 30–50 mm 2–13 mm Pulmonary passage of larvae Yes Yes Yes No No Incubation perioda (days) 60–75 40–100 25–30 70–90 35–45 Longevity 1 year N. americanus: 2–5 years A. duodenale: 6–8 years A. ceylanicum: 6–8 yearsb Fecundity (eggs/day/ worm) 240,000 N. americanus: 9000–10,000 A. duodenale: 10,000–28,000 A. ceylanicum: 5,000–15,000 Principal symptoms Gastrointestinal symptoms; rarely, biliary obstruction or, in heavy infections, gastrointestinal obstruction Iron-deficiency anemia in moderate and heavy infections Diagnosis Eggs in stool Eggs in fresh stool, larvae in old stool Treatment Mebendazole Albendazole Ivermectin Moxidectin Pyrantel pamoate Mebendazole Albendazole aTime from infection to egg production by mature female worm. bAssumed but no evidence base in humans. Clinical Features  During the lung phase of larval migration, ~9–12 days after egg ingestion, patients may develop an irritating nonproductive cough and burning substernal discomfort that is aggravated by coughing or deep inspiration. Dyspnea and bloodtinged sputum are less common. Fever can occur. Eosinophilia develops during this symptomatic phase and subsides slowly over weeks. Chest imaging may reveal rounded infiltrates a few millime­ ters to several centimeters in size that are hallmarks of eosinophilic pneumonitis (Löffler’s syndrome). These infiltrates may be transient and intermittent, clearing after several weeks. Where there is sea­ sonal transmission of the parasite such as on the Arabian peninsula, seasonal pneumonitis with eosinophilia may develop in previously infected and sensitized hosts. In light infections, adult worms in the small intestine usually cause no symptoms. In heavier infections, a large bolus of entangled worms can cause pain and small-bowel obstruction, sometimes complicated by perforation, intussusception, or volvulus. Obstruction is more com­ mon in children due to their having intestinal lumens of narrow diam­ eter. Single worms may cause disease when they migrate into aberrant sites. A large worm can enter and occlude the biliary tree, causing bili­ ary colic, cholecystitis, cholangitis, pancreatitis, or (rarely) intrahepatic abscesses. Migration of an adult worm up the esophagus can provoke coughing or vomiting up the worm. In highly endemic areas, intestinal and biliary ascariasis can rival acute appendicitis as a cause of surgical acute abdomen. Laboratory Findings  Most cases of ascariasis can be diagnosed by microscopic detection of characteristic Ascaris eggs (65 × 45 μm) in

PARASITIC NEMATODE TRICHURIS TRICHIURA (WHIPWORM) ENTEROBIUS VERMICULARIS (PINWORM) STRONGYLOIDES STERCORALIS Oral Oral Cecum, appendix Decades (due to autoinfection) 5 years 2 months 5000–10,000 3000–7000 2000–10,000 Gastrointestinal symptoms; malabsorption or sepsis in hyperinfection Gastrointestinal symptoms, rectal prolapse, or anemia in heavy infection Perianal pruritus CHAPTER 239 Larvae in stool or duodenal aspirate; sputum in hyperinfection; serology Eggs in stool Eggs from perianal skin on cellulose acetate tape Ivermectin Albendazole Mebendazole Albendazole Ivermectin  Mebendazole Albendazole Pyrantel pamoate Intestinal Nematode Infections fecal samples, although increasingly, polymerase chain reaction (PCR) of worm DNA extracted from stool is being used in research and some clinical settings. Occasionally, patients present after passing an adult worm—identifiable by its large size and smooth cream-colored surface— in the stool or, much less commonly, through the mouth or nose. During the early transpulmonary migratory phase, when eosinophilic pneumonitis occurs, larvae can be found in sputum or gastric aspirates before diagnostic eggs appear in the stool. The eosinophilia that is prominent during this early stage usually decreases to minimal levels in established infection. Adult worms may be visualized, occasionally serendipitously, on contrast radiographic studies of the gastrointestinal tract. A plain abdominal film may reveal masses of worms in gas-filled loops of bowel in patients with intestinal obstruction. Pancreaticobili­ ary worms can be detected by ultrasound and endoscopic retrograde cholangiopancreatography; the latter method has been used to extract biliary Ascaris worms. TREATMENT Ascariasis Ascariasis should always be treated to prevent potentially serious complications. Albendazole (400 mg once), mebendazole (100 mg twice daily for 3 days or 500 mg once), pyrantel pamoate (11 mg/kg once with a maximum dose not to exceed 1 g), ivermectin (150–200 μg/kg once), and moxidectin (8 mg once) are effective. These medi­ cations are contraindicated in pregnancy, however. Mild diarrhea and abdominal pain are uncommon side effects of these agents.

Partial intestinal obstruction should be managed with nasogastric suction, IV fluid administration, and instillation of piperazine through the nasogastric tube, although complete obstruction and its severe complications require immediate surgical intervention.

■ ■HOOKWORM Three species (Necator americanus, Ancylostoma duodenale, and Ancylostoma ceylanicum) are responsible for most human hookworm infections. Most infected individuals are asymptomatic. Hookworm disease develops from a combination of factors—heavy worm burden, prolonged duration of infection, and inadequate iron intake—and results in iron-deficiency anemia and, on occasion, hypoproteinemia. Life Cycle  Adult hookworms, which are ~1 cm long, use buccal teeth (Ancylostoma) or cutting plates (Necator) to attach to the smallbowel mucosa where they secrete enzymes that enable them to invade submucosal tissues and ingest blood and villous tissue. Female adult hookworms produce thousands of eggs daily. The eggs are deposited with feces in soil, where rhabditiform larvae hatch and develop over a 1-week period into infectious filariform larvae. Infective larvae pen­ etrate the skin and reach the lungs by way of the bloodstream. There they invade alveoli and ascend the airways to the larynx before being swallowed and reaching the small intestine. The prepatent period from skin penetration to appearance of eggs in the feces is ~6–8 weeks, but it may be longer with Ancylostoma spp. Less commonly, larvae of Ancy­ lostoma spp., if swallowed orally, can survive and develop directly into adult worms that parasitize the intestinal mucosa. Adult hookworms may survive over a decade but usually live ~6–8 years for A. duodenale and 2–5 years for N. americanus. PART 5 Infectious Diseases Epidemiology  Over 400 million people are infected with hook­ worms worldwide. Whereas N. americanus is the predominant spe­ cies throughout the tropics and subtropics, A. duodenale is more geographically restricted to areas of North Africa and northern Asia. A. ceylanicum is much less common than the other two species and is mainly found in Southeast Asia. Age prevalence studies have shown a constant increase in hookworm prevalence throughout childhood and into adulthood. Older children have the greatest intensity of hookworm infection; however, in rural areas where fields are fertil­ ized with human feces, older working adults also may be heavily infected. Clinical Features  Most hookworm infections are of light intensity and therefore are clinically asymptomatic. Infective larvae may pro­ voke a pruritic maculopapular rash (“ground itch”) at the site of skin penetration as well as serpiginous tracks of subcutaneous migration (similar to those of cutaneous larva migrans; Chap. 238) in previously sensitized hosts. Larvae migrating through the lungs occasionally cause mild transient pneumonitis, but this condition develops less frequently in hookworm infection than in ascariasis. In the early intes­ tinal phase, infected persons may develop epigastric pain, abdominal bloating, and other abdominal symptoms accompanied by eosino­ philia. The major consequence of chronic hookworm infection is iron deficiency. Symptoms are minimal if iron stores are adequate, but undernourished individuals develop symptoms of progressive irondeficiency anemia and hypoproteinemia, including fatigue, weakness, and shortness of breath. Laboratory Findings  The diagnosis is established by the finding of characteristic 40 × 60 μm oval hookworm eggs in the feces. Stool concentration techniques may be required to detect light infections. Eggs of the three species are indistinguishable by light microscopy, whereas PCR provides significant improvement in species-specific diagnosis, although this remains a research tool that is not available in commercial laboratories. In a stool sample that is not fresh, hookworm eggs may have hatched to release rhabditiform larvae, which must be differentiated from those of S. stercoralis. Hypochromic microcytic anemia, occasionally with eosinophilia or hypoalbuminemia, is char­ acteristic of hookworm disease.

TREATMENT Hookworm Infection Hookworm infection can be treated with several safe and effective anthelmintic drugs, including albendazole (400 mg once daily for

3 days) and mebendazole (500 mg once daily or 100 mg twice daily for 3 days). Mild iron-deficiency anemia can often be treated with oral iron supplementation alone. Severe hookworm disease with protein loss and malabsorption necessitates nutritional support and oral iron replacement along with deworming. There is significant concern that the benzimidazoles (mebendazole and albendazole) are becoming much less effective against human hookworms. Ancylostoma caninum and Ancylostoma braziliense  A. caninum, the canine hookworm, has been identified as a cause of human eosino­ philic enteritis, especially in northeastern Australia. In this rare zoo­ notic infection, adult hookworms attach to the small intestine (where they may be visualized by endoscopy) and elicit abdominal pain and intense local eosinophilia. Treatment with mebendazole (100 mg twice daily for 3 days) or albendazole (400 mg once) or endoscopic removal is effective. Both of these animal hookworm species can cause cutane­ ous larva migrans (“creeping eruption”; Chap. 238). ■ ■STRONGYLOIDIASIS S. stercoralis is distinguished by its ability—unique among helminths (except for Capillaria; see below)—to complete its life cycle and repli­ cate within a human host. This capacity permits ongoing cycles of auto­ infection as infective larvae are internally produced that can develop into egg-producing adult worms without exiting the host. Infection with S. stercoralis can thus persist for decades without further exposure to exogenous infective larvae. In immunocompromised hosts, large numbers of invasive Strongyloides larvae can disseminate widely and can be fatal. Life Cycle  In addition to a parasitic life cycle in the human host, Strongyloides can undergo a free-living cycle of development in the soil (Fig. 239-1). This adaptability facilitates the parasite’s survival in the absence of mammalian hosts. Rhabditiform larvae passed in feces can transform into infectious filariform larvae either directly or after a free-living phase of development. Humans acquire S. stercoralis when filariform larvae in fecally contaminated soil penetrate the skin or mucous membranes. The larvae then travel through the bloodstream to the lungs, where they break into the alveolar spaces, ascend the bronchial tree, are swallowed, and thereby reach the small intestine. There the larvae mature into adult worms that embed in the mucosa of the proximal small bowel. The minute (1- to 2-mm long) parasitic adult female worms reproduce by parthenogenesis; adult males do not exist in the human host. Eggs hatch in the intestinal mucosa, releasing rhabditiform larvae that migrate to the lumen and pass with the feces into soil. Alternatively, rhabditiform larvae in the bowel can develop directly into filariform larvae that penetrate the colonic wall or perianal skin and enter the circulation to repeat the migration that establishes ongoing internal reinfection. Epidemiology  S. stercoralis is spottily distributed in tropical areas and other warm, humid regions and is common in Southeast Asia, subSaharan Africa, and Brazil. In the United States, the parasite is endemic in parts of the Southeast and is found in immigrants, refugees, travel­ ers, and military personnel who have lived in endemic areas. Clinical Features  In uncomplicated strongyloidiasis, many patients are asymptomatic or have mild cutaneous and/or abdominal symptoms. Recurrent urticaria, often involving the buttocks, is the most common cutaneous manifestation. Larvae migrating in the skin can elicit a pathognomonic serpiginous eruption known as larva cur­ rens. This pruritic, raised, erythematous lesion advances as rapidly as 10 cm/h along the course of larval migration. Adult parasites burrow into the duodenojejunal mucosa and can cause abdominal (usually midepigastric) pain, which resembles peptic ulcer disease except that

Larvae migrate via bloodstream or lymphatics to lungs, ascend airway to trachea and pharynx, and are swallowed. Hyperinfection: With immunosuppression, larger numbers of filariform larvae develop, penetrate bowel, and disseminate, causing: Filariform larvae (450 µm) Rhabditiform larvae in soil FIGURE 239-1  Life cycle of Strongyloides stercoralis. (Reproduced with permission from RL Guerrant et al [eds]: Tropical Infectious Diseases: Principles, Pathogens and Practice, 2nd ed. Elsevier, 2006.) it is aggravated by food ingestion. Nausea, watery diarrhea, abdominal bloating, occult gastrointestinal bleeding, and weight loss can occur. Small-bowel obstruction may develop with early, heavy infection. Pul­ monary symptoms are rare in uncomplicated strongyloidiasis. Eosino­ philia is common, with levels fluctuating over time. The ongoing autoinfection cycle of S. stercoralis is normally con­ strained by the host’s immune system. Impairment of host cellmediated immunity, especially with high-dose glucocorticoid therapy and less commonly with other immunosuppressive medications, or associated with infection with human T-cell lymphotropic virus type 1 (HTLV-1), may lead to hyperinfection and the generation of large numbers of filariform larvae. Colitis, enteritis, or malabsorption may develop. Hyperinfection can also lead to disseminated strongyloidiasis, characterized by larvae invading not only gastrointestinal tissues and the lungs but also the central nervous system, skin, peritoneum, liver, and kidneys. Moreover, bacteremia may develop because of the spread of enteric flora through disrupted mucosal barriers. Gram-negative sepsis, pneumonia, or meningitis may complicate or dominate the clinical course. Eosinophilia is often absent in severely infected patients. Dis­ seminated strongyloidiasis, particularly in patients with unsuspected infection who are taking glucocorticoids, has a high mortality rate. Diagnosis  In uncomplicated strongyloidiasis, visualizing rhab­ ditiform larvae by light microscopic examination of a fecal sample is diagnostic. Rhabditiform larvae are ~250 μm long, with a short buccal cavity that distinguishes them from hookworm larvae. In uncom­ plicated infections, few larvae are passed and single stool examina­ tions detect only about one-third of cases. Serial examinations and the use of the agar plate detection method improve the sensitivity of stool diagnosis. Again, PCR has begun to be used more widely and provides increased diagnostic sensitivity. In hyperinfection, a single

2-mm hermaphroditic adult s penetrate small-bowel mucosa and release eggs, which hatch to rhabditiform larvae. Lung or intestinal stage may cause: Eosinophilia and intermittent epigastric pain Autoinfection: Transform within the intestine into filariform larvae, which penetrate perianal skin or bowel mucosa, causing: Rhabditiform larvae (250 µm) Pruritic larva currens Eosinophilia Larvae shed in stool Colitis, polymicrobial sepsis, pneumonitis, or meningitis Free-living 1-mm adults in soil CHAPTER 239 Direct development Eggs in soil Indirect development (heterogonic) (can multiply outside host for several generations) in soil Intestinal Nematode Infections microscopy-based stool examination is usually positive given the large number of larvae being produced. Strongyloides larvae may also be found by sampling of the duodenojejunal contents by aspiration or biopsy. An enzyme-linked immunosorbent assay for serum antibod­ ies to antigens of Strongyloides is a sensitive method for diagnosing uncomplicated infections. Such serologic testing should be performed for patients with prior potential exposure, especially those with eosino­ philia and/or those who may be starting glucocorticoid therapy or undergoing solid organ transplantation. In disseminated strongyloi­ diasis, filariform larvae are easily detected in stool as well as in samples obtained from sites of potential larval migration, including sputum, bronchoalveolar lavage fluid, or surgical drainage fluid. TREATMENT Strongyloidiasis Even in the asymptomatic state, strongyloidiasis must be treated because of the potential for subsequent hyperinfection and fatal dissemination. Ivermectin (200 μg/kg daily for 2 days) is more effective than albendazole (400 mg daily for 3 days). Decreases in eosinophil count and antibody titer indicate a response to treat­ ment. For disseminated strongyloidiasis, treatment with ivermectin should be extended for at least 14 days after fecal examinations have become negative. In potentially immunocompromised hosts, the course of ivermectin should be repeated 2 weeks after initial treatment. Ivermectin has been successfully given per rectum in those unable to take ivermectin orally and can be given parenterally (using veterinary preparations) through single-patient expanded access protocols.

■ ■TRICHURIASIS Most infections with Trichuris trichiura are asymptomatic, but heavy infections may cause gastrointestinal symptoms. Like the other soiltransmitted helminths, whipworm is distributed globally in the trop­ ics and subtropics and is most common among poor children from resource-limited regions of the world.

Life Cycle  Adult Trichuris worms reside in the colon and cecum, their thin anterior portions embedded in the superficial mucosa. Thousands of eggs laid daily by adult female worms pass with the feces and mature in the soil. After ingestion, infective eggs hatch in the duodenum, releasing larvae that mature before migrating to the large bowel. The entire cycle takes ~3 months, and adult worms may live for several years. Clinical Features  Most individuals infected with T. trichiura have no symptoms or eosinophilia. Heavy infections may result in anemia, abdominal pain, anorexia, and bloody or mucoid diarrhea resembling inflammatory bowel disease. Rectal prolapse can result from massive infections in children due to protracted tenesmus. Moderately heavy T. trichiura burdens also contribute to impaired physical growth. Diagnosis and Treatment  The characteristic 50 × 20 μm lemonshaped T. trichiura eggs are readily detected on microscopic examina­ tion of stool. Adult worms, which are 3–5 cm long, are occasionally seen on proctoscopy. PCR is being used increasingly in settings where it is available. Albendazole (400 mg daily for 3 days) or mebendazole (100 mg twice daily for 3 days) is safe and moderately effective for treatment. The addition of ivermectin (200 μg/kg daily for 3 doses) to either benzimidazole drug increases cure rates significantly. PART 5 Infectious Diseases ■ ■ENTEROBIASIS (PINWORM) E. vermicularis is more common in temperate climates than in the tropics. In the United States, ~40 million persons are infected with pinworms, with most cases occurring in children. Life Cycle and Epidemiology  Adult Enterobius worms are ~5–10 mm long and dwell in the cecum. Gravid female worms migrate nocturnally out of the anus to the perianal region where they release up to 10,000 immature eggs each. The eggs become infective within hours and are transmitted by hand-to-mouth passage. From ingested eggs, larvae hatch and mature into adults. This life cycle takes ~1 month, and adult worms survive for ~2 months. Autoinfection results from perianal scratching and transport of infective eggs on the fingers or under the nails to the mouth. Retroinfection can also occur by larvae released from embryonated eggs on the perianal skin migrating back into the rectum. Because of the ease of person-to-person spread, pin­ worm infections are common among family members. Clinical Features  Most pinworm infections are asymptomatic. Perianal pruritus is the cardinal symptom. The itching, which is often worse at night as a result of the nocturnal emergence of female worms, may lead to excoriation and bacterial superinfection. Heavy infections have been associated with abdominal pain, weight loss, and rarely acute appendicitis. Uncommonly, pinworms may migrate into the female genital tract, causing vulvovaginitis and pelvic or peritoneal granulo­ mas. Eosinophilia is uncommon. Diagnosis  Since pinworm eggs are not released in feces, the diagno­ sis cannot be made by conventional fecal ova and parasite microscopy. Instead, eggs are detected by the application of clear cellulose acetate tape to the perianal region in the morning. After the tape is transferred to a slide, microscopic examination can detect pinworm eggs, which are oval, measure 55 × 25 μm, and are flattened along one side. TREATMENT Enterobiasis Infected children and adults should be treated with mebendazole (100 mg once), albendazole (400 mg once), or pyrantel pamoate

(11 mg/kg once), with the same treatment repeated after 2 weeks because the drugs do not kill eggs or early-stage larvae. Treatment of household members is recommended to eliminate asymptomatic reservoirs of potential reinfection. Linens and clothing should be washed in hot water followed by a hot dryer to kill deposited eggs. ■ ■TRICHOSTRONGYLIASIS Trichostrongylus species, which are normally parasites of herbivorous animals, occasionally infect humans, particularly in Asia, Africa, and Australia. Humans acquire the infection by accidentally ingesting Trichostrongylus larvae on contaminated leafy vegetables. The larvae do not migrate in humans but mature directly into adult worms in the small bowel. The pathology caused by these worms is similar to hookworm, although they ingest far less blood. Most infected persons are asymptomatic, but heavy infections may give rise to mild anemia and eosinophilia. In stool examinations, Trichostrongylus eggs resemble hookworm eggs but are larger (85 × 115 μm). Treatment consists of mebendazole, albendazole, or pyrantel pamoate (Chap. 229). ■ ■ANISAKIASIS Anisakiasis is a gastrointestinal infection caused by the accidental ingestion in uncooked saltwater fish of nematode larvae belonging to the family Anisakidae. The incidence of anisakiasis in the United States has increased as a result of the growing popularity of raw fish dishes. Most cases occur in Japan, the Netherlands, and Chile, where raw fish—sashimi, pickled green herring, and ceviche, respectively— are national culinary staples. Anisakid nematodes parasitize large sea mammals such as whales, dolphins, and seals. As part of a complex parasitic life cycle involving marine food chains, infectious larvae migrate to the musculature of a variety of fish species that serve as intermediate hosts. Both Anisakis simplex and Pseudoterranova decipiens have been implicated in human anisakiasis, but an identi­ cal gastric syndrome may be caused by the red larvae of eustrongylid parasites of fish-eating birds. When humans consume infected raw or undercooked fish, live larvae may be coughed up within 48 h. Alternatively, larvae may immediately penetrate the mucosa of the stomach. Within hours, vio­ lent upper abdominal pain accompanied by nausea and occasionally vomiting ensues, mimicking an acute abdomen. The diagnosis can be established by direct visualization on upper endoscopy, outlining of the worm by contrast radiographic studies, or histopathologic exami­ nation of extracted tissue. Extraction of the burrowing larvae during endoscopy is curative. In addition, larvae may pass to the small bowel, where they penetrate the mucosa and provoke a vigorous eosinophilic granulomatous response. Symptoms may appear 1–2 weeks after the infective meal, with intermittent abdominal pain, diarrhea, nausea, and fever resembling the manifestations of Crohn’s disease. Ingestion of Anisakis-derived proteins through consumption of fish meat con­ taining Anisakis parasites can elicit allergic gastrointestinal and even anaphylactic responses. Anisakid eggs are not found in the stool since the larvae do not mature in humans. Serologic tests have been developed but are not widely available. Anisakid larvae in saltwater fish are killed by cooking to 60°C, freez­ ing at –20°C for 3 days, or commercial blast freezing, but usually not by salting, marinating, or cold smoking. No medical treatment is available; surgical or endoscopic removal should be undertaken. ■ ■CAPILLARIASIS Intestinal capillariasis is caused by ingestion of raw fish infected with Capillaria philippinensis. Subsequent autoinfection can lead to a severe wasting syndrome. The disease occurs in the Philippines and Thailand and, on occasion, elsewhere in Asia. The natural life cycle of C. philippinensis involves fish from fresh and brackish water. When humans eat infected raw fish, the larvae mature in the intestine into adult worms, which produce invasive larvae that cause intestinal inflammation and villus loss and can develop into new adult worms without leaving the human host. Capillariasis has an insidious onset