CHAPTER OUTLINE Videos for this chapter can be found on www.expertconsult.com.
Parasitic worms are found worldwide. Modern travel, emigration,[1] and consumption of “exotic” cuisines allow intestinal helminths to appear in any locale. People now acquire tropical helminths without leaving their industrialized temperate cities. Travel history is a critical, but often overlooked, aspect of the patient interview. Many helminths survive for decades within a host, so even a remote history of visits to or emigration from countries where they are endemic is important. Fresh food is flown around the world and often consumed raw.
Physicians need to remain alert to the possibility of infection with these organisms because some cause severe disease that requires years to develop or occurs only under special circumstances. For example, patients might have occult Strongyloides stercoralis until treatment with glucocorticoids causes fulminant disease, occult Clonorchis sinensis until they develop cholangiocarcinoma, or occult Schistosoma mansoni until they develop portal hypertension and bleeding from esophageal varices.
In developed countries, we usually diagnose an intestinal helminth because we stumble across it rather than because we actively pursue it. Helminths are complex organisms well adapted to their hosts; like quiet house guests, most cause no symptoms. Worms rarely cause diarrhea, but many medical laboratories do not assay formed stool routinely for parasite eggs. Physicians need to communicate their concerns of possible helminthic infection to laboratory personnel. A telephone call to the local laboratory before a sample is sent can improve diagnostic results dramatically. Occasionally, alarmed patients bring proglottids or whole worms that they passed with their stools. These specimens should be fixed in 5% aqueous formalin and sent for identification.[2] All specimens should be handled carefully with full precautions to avoid accidental exposure. Some helminthic infections are difficult to diagnose, especially when the worm burden is light. Diagnosis can require serologic evaluation, analysis of multiple stools, or use of concentration techniques in addition to a high level of physician awareness. For example, S. stercoralis eggs do not appear in the stool, and diagnosis is best made serologically. Ancyclostoma caninum causes eosinophilic enteritis but does not lay eggs when infecting people. Some helminths can cause severe disease, but this is unusual. Most persons colonized with helminths have no symptoms or illness attributable to the parasites. Only with heavy infections does disease result. Well-adapted worms usually act more as commensals than as pathogens. It is even possible that exposure to helminths affords some protection against disease due to excessive immune reactions.[3,4] Helminths induce immune regulatory pathways.[5] Recent studies in mice and rats show that exposure to helminths can be used to prevent or treat colitis,[3,6-8] insulin-dependent diabetes,[9] and autoimmune encephalitis.[10,11] Studies in humans show that helminth exposure improves ulcerative colitis[12] and probably Crohn's disease[13,14] and that helminth eradication increases atopy.[15] Although it remains important to treat helminthic infections when they are discovered, further research on these organisms can enable discovery of new approaches to treat immune-mediated disease. This chapter is divided into three sections: nematodes (roundworms), cestodes (tapeworms), and trematodes (flukes or flatworms). For the most part, each worm is addressed separately, noting its epidemiology, life cycle, clinical manifestations, diagnosis, and treatment. NEMATODES ASCARIS LUMBRICOIDES Ascaris lumbricoides is the largest of the nematode parasites that colonize humans. Females can grow to 49 cm (19 inches).[16] The name “lumbricoides” alludes to its resemblance to earth worms (Lumbricus sp.). The parasite is acquired by ingesting its eggs. Ascaris can cause intestinal obstruction and pancreaticobiliary symptoms. Treatment is albendazole. Epidemiology A. lumbricoides has a worldwide distribution, although these parasites are most numerous in less-developed countries and in areas with poor sanitation. About 25% of the world's population (1.2 billion people) harbor A. lumbricoides.[17,18] Children acquire the parasite by playing in dirt contaminated with eggs, whereas adults most often are infected by farming or eating raw vegetables from plants fertilized with untreated sewage. Pigs harbor Ascaris suum, which is closely related to A. lumbricoides, but cross-infection is rare.[19]Life Cycle Humans acquire the parasite by ingesting embryonated eggs that contain third-stage larvae. Freshly deposited fertilized eggs incubate in the soil for 10 to 15 days while the embryo develops and molts twice. The eggs become infective after this incubation period. The eggs are remarkably stable, can survive freezing, and can remain viable for seven to 10 years. The eggs are resistant to most chemical treatments including pickling, but they rapidly die in boiling water. Once ingested, eggs hatch in the duodenum and release their larvae, which penetrate the intestinal wall and enter the mesenteric venules and lymphatics. Larvae migrating with portal blood pass to the liver, through the sinusoids to the hepatic veins, and then through the right side of the heart to enter the lungs. Larvae migrating via the lymphatics pass through mesenteric lymph nodes to the thoracic duct and enter the superior vena cava to arrive in the lungs. The larvae then lodge in the pulmonary capillaries and break into the alveoli, where they molt twice while growing to 1.5 mm in length. Larvae then ascend the tracheobronchial tree, and arrive in the hypopharynx, they are again swallowed, and pass into the small intestine, where they molt again and finally mature. Mature male A. lumbricoides are smaller (10 to 30 cm) than females (20 to 49 cm). Worms mate in the small intestine and females deposit about 200,000 eggs a day. Adult worms live for about one year (six to 18 months). Because their eggs require incubation in the soil to become infective, Ascaris does not multiply in the host. Continued infestation requires repeat ingestion of embryonated eggs. Clinical Features and Pathophysiology A. lumbricoides produces no symptoms in most infected persons. Often, worms are found unexpectedly on endoscopy[20,21] (Video 110-1) or are seen on radiologic imaging,[22] or eggs are identified in stool specimens of patients with symptoms not directly attributable to the worms. Disease usually develops only in those with heavy worm burdens: pulmonary, intestinal, and hepatobiliary ascariasis are well described. Pulmonary ascariasis (Ascaris pneumonia) develops four to 16 days after ingesting infective eggs. The larvae migrate into the alveoli and elicit an inflammatory response that can cause consolidation. The pneumonia usually is self-limited but can be life-threatening. Large numbers of mature worms can cause severe intestinal symptoms including abdominal pain, distention, nausea, and vomiting. The most common complication of intestinal ascariasis is partial or complete small bowel obstruction; such patients often have a history of passing mature worms in their stool or vomitus. Patients with intestinal obstruction generally have more than 60 worms,[23] and the rare patients with fatal cases often have more than 600 worms. Fatality results from intestinal necrosis caused by obstruction, intussusception, or volvulus (Fig. 110-1).[24] Most cases of obstruction, absent signs of peritonitis or perforation, can be managed conservatively.
A. lumbricoides are highly motile. Mature worms can enter the ampulla of Vater (Fig. 110-2) and migrate into the bile or pancreatic ducts, causing biliary colic, obstructive jaundice, ascending cholangitis, acalculous cholecystitis, or acute pancreatitis.[16] Pregnancy can promote biliary trespass.[25] The worms can move in and out of the papilla, producing intermittent symptoms and fluctuating laboratory tests. Recurrent ascending cholangitis or acute pancreatitis from ascariasis is rare in highly developed Western countries but can be fatal if the diagnosis is not entertained.[26]
Diagnosis Often it is an alarmed patient who discovers Ascaris after passing a motile adult worm with a bowel movement. The worms, however, usually do not cause diarrhea. Most patients do not have specific symptoms or eosinophilia. Ascaris eggs are visible in direct smears of stool (Fig. 110-3). The eggs begin to appear in the stool about two months after initial exposure. Fertilized eggs are 35 by 55 ?m and have a thick shell and outer layer; females also lay unfertilized eggs that are larger (90 by 44 ?m) and have a thin shell and outer layer. Ascaris eggs that lose their outer layer resemble the eggs of hookworms.
Adults worms may be seen at endoscopy,[21] or identified on upper gastrointestinal series as long, linear, filling defects within the small intestine.[22] The worms retain barium after it has cleared from the patient's gastrointestinal tract, producing linear opacities. Similar findings are seen on endoscopic retrograde cholangiopancreatography (ERCP) if a worm is in the bile or pancreatic duct (Fig. 110-4). Ascaris also has a characteristic appearance on ultrasound examination of the biliary tree or pancreas: They appear as long, linear echogenic strips that do not cast acoustic shadows.[22]
Treatment Asymptomatic colonization with A. lumbricoides is treated easily with a single 400-mg oral dose of albendazole. Albendazole inhibits glucose uptake and microtubule formation, effectively paralyzing the worms. Albendazole is poorly absorbed but is teratogenic, and therefore it should not be used in pregnant women. When possible, treatment with this agent should be delayed until after delivery. Single-dose mebendazole also is efficacious for Ascaris.[27] A study of 1042 pregnant women in Peru found no adverse effect of a single 500-mg oral dose of mebendazole on birth outcomes.[28] Patients with pulmonary ascariasis should be treated with glucocorticoids to reduce the pneumonitis and be given two 400-mg doses of albendazole one month apart. Because albendazole is poorly absorbed, ascaricidal tissue concentrations are not achieved. The first dose kills mature worms that finished migrating to the intestine, and the second dose kills worms that were in transit when the first dose was given. Albendazole can cause nausea, vomiting, and abdominal pain. Intestinal ascariasis with obstruction often can be treated conservatively with fluid resuscitation, nasogastric decompression, antibiotics, and one dose of albendazole. Surgery is not required unless the patient develops signs of volvulus, intussusception, or peritonitis. If the bowel is viable, an enterotomy allows intraoperative removal of worms. Albendazole may be held until after the obstruction resolves and then used to eradicate any remaining organisms. Hepatobiliary ascariasis also can be treated conservatively with fluid resuscitation, bowel rest, and antibiotics.[29] Worms in the bile duct are not effectively treated with albendazole because it is poorly absorbed and not concentrated in the bile. This feature of albendazole is advantageous because were paralyzed worms unable to pass through the sphincter of Oddi, they could become trapped in the bile duct. Patients with hepatobiliary ascariasis should be treated with albendazole each day for several days because the worms only become susceptible when they migrate out of the bile duct. Worms also can invade the pancreatic duct and can be treated conservatively, as for hepatobiliary ascariasis.[30] Ascending cholangitis, acute obstructive jaundice, or acute pancreatitis requires emergent ERCP with worm extraction from the ducts by balloon, basket, or forceps—preferably without sphincterotomy. Ampullary sphincterotomy permits worms easier access to the ducts and can increase the risk of recurrent pancreaticobiliary ascariasis.[31]STRONGYLOIDES STERCORALIS S. stercoralis is a free-living tropical and semitropical soil helminth, the filariform larvae of which can penetrate intact skin. As a parasite, Strongyloides lives in the intestine and lays eggs that hatch while still in the bowel. Filariform larvae develop within the intestine, migrate along defined paths, and mature to increase the number of adult parasites in the host. Immunosuppression and glucocorticoid treatment cause a fulminant reproduction of parasites that can prove fatal. Treatment is ivermectin. Epidemiology S. stercoralis is endemic in tropical and semitropical regions, but it can also be acquired in rural southeastern United States and northern Italy. Strongyloides exists as a free-living organism that does not require a host to replicate. Improved sanitation does not remove the risk of acquiring the parasite from soil. Patients from endemic areas, military veterans who served in Asia, and prisoners of war are at high risk for subclinical strongyloidiasis. Life Cycle Adult male and female S. stercoralis live in the soil and lay eggs that hatch rhabditiform larvae. Rhabditiform larvae develop in the soil into mature adults to complete the life cycle of this worm. Rhabditiform larvae (250 ?m) also can develop into longer (500 ?m) infective filariform larvae that can penetrate any area of skin contacting soil, after which they migrate through the dermis to enter the vasculature. The larvae circulate with the venous blood until they reach the lungs, where they break into the alveoli and ascend the bronchial tree. The worms then are swallowed with bronchial secretions and pass into the small intestine, where they embed in the jejunal mucosa and mature. Female S. stercoralis can lay fertile eggs by parthenogenesis and therefore do not require males to reproduce. The eggs hatch within the small intestine, and rhabditiform larvae migrate into the lumen. Rhabditiform larvae, not eggs, are passed in the stool. A critical feature of S. stercoralis infestation is that some rhabditiform larvae sporadically develop into infective filariform larvae within the intestine. Filariform larvae are able to reinfest (autoinfect) the patient, thereby increasing the parasite burden and permitting prolonged colonization so that subclinical strongyloidiasis can exist for many decades after the host has left an endemic area. Clinical Features and Pathophysiology Most patients with S. stercoralis have no abdominal symptoms. Patients might have a serpiginous urticarial rash (larva currens) caused by the rapid (5 to 10 cm/hour) dermal migration of filariform larvae. This rash often occurs on the buttocks from larvae entering the perianal skin after they exit the anus during autoinfection. A study of prisoners of war found this creeping eruption to be a far more common symptom of chronic strongyloidiasis than were gastrointestinal complaints.[32] Occasionally, patients have nausea, abdominal pain, or unexplained occult gastrointestinal blood loss from S. stercoralis. The parasite also can cause colonic inflammation that resembles ulcerative colitis but is more right-sided and strongly eosinophilic.[33-35] While the parasite burden remains balanced, symptoms are minimal or absent. Immunosuppression or glucocorticoid administration upsets this balance. Previously asymptomatic, but chronically infested, patients develop fulminant, potentially fatal strongyloidiasis due to massive autoinfection.[36,37] The mechanisms that permit massive autoinfection are unknown, but events that inhibit Th2-directed immune responses can release eosinophil-mediated control of the parasites. In addition, glucocorticoids can act directly on the parasites to increase the development of infective filariform larvae.[38] Fulminant disseminated strongyloidiasis rarely complicates HIV and AIDS.[39] Massive autoinfection produces disseminated fulminant strongyloidiasis. Migrating filariform larvae injure the intestinal mucosa and carry luminal bacteria into the bloodstream, resulting in polymicrobial sepsis with enteric organisms. Streptococcus bovis endocarditis or meningitis[40] also can result. Numerous larvae migrating through the lungs cause pneumonitis, and worms can arrive in unusual locations such as the brain. Fulminant strongyloidiasis often is fatal. Diagnosis A recent survey of United States physicians-in-training demonstrated very poor ability to identify or even consider strongyloidiasis.[41] Patients with chronic strongyloidiasis often are asymptomatic. Peripheral blood eosinophils may be elevated, but a normal eosinophil count does not argue against infestation with the parasite. Currently, the best method for detecting exposure is enzyme-linked immunosorbent assay (ELISA) for immunoglobulin (Ig) G antibodies against S. stercoralis. This assay is performed by the Centers for Disease Control and Prevention (CDC) in the United States and is 95% sensitive,[42] sensitivity being highest for immigrants with prolonged exposure and lowest for returning visitors with lower-level recently acquired infestation.[43] False-positive reactions can occur in patients exposed to other helminthic parasites,[44] and serologic positivity can indicate prior exposure to S. stercoralis, not necessarily active infestation. Because chronic strongyloidiasis can remain subclinical and difficult to detect for decades, however, treatment of seropositive patients is warranted. Indeed, some argue that patients with only suspected strongyloidiasis, such as immigrants from endemic countries who have elevated eosinophil counts, should be treated empirically before glucocorticoid therapy.[45] Active infestation can be diagnosed by finding rhabditiform larvae in direct smears of the stool, though this is an insensitive method. A 10-fold more sensitive technique is to spread stool on an agar plate and look for serpentine tracks left by migrating larvae.[46] Intestinal biopsy is also an insensitive means of diagnosis. Treatment Chronic strongyloidiasis is best treated with one dose of ivermectin (200 ?g/kg) given orally; this dose is used in both adult and pediatric patients. Ivermectin is better tolerated than thiabendazole. Ivermectin paralyzes the intestinal adult worms but not the larvae migrating through tissue, and therefore patients can develop recurrent infestation from migrating larvae; a repeat dose after two weeks helps to prevent this outcome. Successful treatment causes a fall in antibody titer by six months in most (about 90%) patients.[42] Immunocompromised patients require repeat doses given 2, 15, and 16 days after the first dose.[37]CAPILLARIA (PARACAPILLARIA) PHILIPPINENSIS Capillariasis is acquired by eating raw fish that are infested with the parasite.[47] The nematode causing capillariasis has been renamed from Capillaria philippinensis to Paracapillaria philippinensis,[48] but by any name, it is deadly. The parasite replicates in the host, producing an ever-increasing number of intestinal worms. Patients develop protein-losing, sprue-like diarrhea with progressive emaciation and anasarca, which ultimately leads to death. Treatment is albendazole. Epidemiology The first known human case of capillariasis was reported in 1964. It remains a rare but deadly parasitic infestation. From 1965 through 1968, an epidemic in the rural Philippines involved 229 cases, with an overall mortality rate of 30%.[49] As the name implies, Paracapillaria phillippinensis is endemic to the Philippines, but it also is endemic in Thailand and cases occur in Japan, Taiwan, Egypt, and Iran. Modern travel transports cases worldwide.[50]Life Cycle Birds, not humans, are the natural hosts for P. philippinensis. In the avian small intestine, the larvae mature into adults. The adults are very small, measuring up to 3.9 mm for males and 5.3 mm for females. Adult worms mate and produce eggs. Eggs are deposited in bird droppings into ponds and rivers and are swallowed by fish to complete the life cycle. People become infested with the worm by eating raw or undercooked freshwater or brackish-water fish that contain the parasitic larvae. Some female adult P. philippinensis are larviparous, producing infective larvae instead of eggs. These larvae then mature in the small intestine and increase the parasite burden. This pathway of autoinfection permits a massive increase in parasite numbers. A rhesus monkey originally fed 27 larvae had more than 30,000 worms by 162 days of infection.[51]Clinical Features and Pathophysiology Capillariasis produces a progressive sprue-like illness. Symptoms begin with vague abdominal pain and borborygmi. Two or three weeks after infection, patients begin to have diarrhea. Initially intermittent, diarrhea becomes persistent and increasingly voluminous. Patients rapidly waste from escalating steatorrhea and protein-losing enteropathy. Eventually they manifest emaciation, anasarca, and hypotension; diarrhea produces severe hypokalemia. If untreated, patients die from cardiac failure or secondary bacterial sepsis usually about two months after the initial onset of symptoms. The progressive disease is believed to result from an ever-increasing number of poorly adapted intestinal parasites. In autopsy studies, the jejunal intestinal mucosa showed flattened, denuded villi with numerous plasma cells, lymphocytes, macrophages, and neutrophils infiltrating the lamina propria.[47]Diagnosis Diagnosis is made by finding eggs and larvae in stool specimens. No serologic tests for capillariasis are available. Symptomatic patients have detectable eggs in their stool. The eggs are easily confused with those of Trichuris trichiura, but T. trichiura eggs have prominent bipolar plugs that appear cut off in P. phillipinensis.[47]Treatment Capillariasis requires extended anthelminthic treatment with albendazole 200 mg orally twice daily for 10 days or mebendazole 200 mg orally twice daily for 20 days to prevent recurrence. Albendazole is better tolerated than mebendazole, which can cause headache, diarrhea, and abdominal pain. Extended treatment is necessary because larvae are resistant to these agents. HOOKWORMS (NECATOR AMERICANUS, ANCYLOSTOMA DUODENALE, AND ANCYLOSTOMA CANINUM) Worldwide, an estimated 740 million people are infested with hookworm,[17] usually by Necator americanus, Ancylostoma duodenale, or a mixture of the two. Hookworm is acquired by skin contact with contaminated soil. Moderate infestation contributes to iron deficiency. Hookworm should be suspected in patients with eosinophilia and iron-deficiency anemia. The dog and cat parasite Ancylostoma caninum is a cause of eosinophilic enteritis. Treatment is albendazole. Necator americanus and Ancylostoma duodenale Epidemiology The geographic distribution of N. americanus and A. duodenale extensively overlap, but N. americanus predominates in the Americas, South Pacific, Indonesia, southern India, and central Africa, whereas A. duodenale is more common in North Africa, the Middle East, Europe, Pakistan, and northern India. Hookworm infestation is acquired by contacting soil contaminated with human waste. Hookworm is endemic in tropical to warm temperate areas that lack sufficient sewage facilities. Indigenous hookworm infestation largely has been eradicated in the United States, although small pockets of transmission still exist. Life Cycle Infective third-stage hookworm larvae penetrate intact skin, such as between the toes of bare feet while walking on contaminated ground. Larvae migrate through the dermis to reach blood vessels. This migration can cause a pruritic, serpiginous rash, cutaneous larva migrans (Fig. 110-5). Ancylostoma braziliense normally infests dogs and cats, but it produces a similar rash during infective dermal wandering in humans and is the usual cause of cutaneous larva migrans. Larvae of N. americanus and A. duodenale enter blood vessels in the skin and migrate with venous flow through the right side of the heart to the lungs. A. duodenale larvae can arrest their migration and become dormant for many months before proceeding to the lungs.[52] In the lungs, larvae penetrate the alveoli and enter the air spaces, after which they migrate up the pulmonary tree, are swallowed with saliva, and pass into the small intestine, where they mature. Patients also can acquire A. duodenale by directly ingesting larvae crawling on contaminated fresh vegetables. Adult worms develop large buccal cavities and graze on the intestinal mucosa, ingesting epithelial cells and blood (Figs. 110-6 and 110-7). Adults are about one centimeter long and can live for up to 14 years. Mature worms mate and lay eggs. Each female N. americanus lays about 10,000 eggs a day, and each female A. duodenale lays about 20,000 eggs a day. Eggs are deposited with feces in moist, shady soil, where they hatch to release larvae. The larvae molt twice after which they move to the soil surface and seek a suitable host.
Clinical Features and Pathophysiology Light infestations with N. americanus and A. duodenale cause no symptoms.[53] The major consequence of moderate and heavy hookworm infestation is iron deficiency. Adult worms feed on intestinal epithelial cells and blood. The closely related A. caninum (see later) secretes anticoagulant peptides that inhibit clotting factors[54] and platelet aggregation,[55] thereby preventing hemostasis and permitting the hematophagous parasites to feed on host blood. Intestinal blood loss is estimated to be 0.01 to 0.04 mL/day per adult N. americanus and 0.05 to 0.3 mL/day per adult A. duodenale.[56] With a moderate number of worms, this blood loss becomes appreciable (Table 110-1). Iron deficiency results when iron loss outstrips iron absorption. The average North American diet is high in iron so anemia might not develop, and men with a diet high in iron (more than 20 mg/day) can tolerate up to 800 adult hookworms without developing anemia.
Table 110-1 -- A Comparison of Daily Physiologic Iron Losses and Iron Losses Due to Hookworm Infection in Women*
Infestation with hookworm can modulate immune responses.[57] Clinical trials are under way to determine if subclinical infestation with hookworm inhibits immune-mediated disease such as Crohn's disease and asthma.[58,59] Dose-ranging studies on healthy volunteers suggested that low-level hookworm infestation (10 larvae) is well tolerated.[58]Diagnosis Hookworms can be visible endoscopically (Fig. 110-8),[60] but diagnosis is made by identifying eggs on direct smears of formalin-fixed stool (see Fig. 110-3). Evaluation of three stool specimens obtained on separate days should permit diagnosis of hookworm,[61] but light infestations can require concentration techniques. Eggs mature rapidly at room temperature and can hatch to release larvae. It is difficult to distinguish N. americanus eggs from those of A. duodenale simply by morphology.
Treatment Albendazole 400 mg given orally as a single dose is adequate treatment for hookworm. Mebendazole 100 mg given orally twice daily for three days also is effective but not as well tolerated. A. duodenale larvae can remain in a dormant state for months before maturing and causing relapse, a situation that is treated with a repeat course of albendazole or mebendazole. Ancylostoma caninum Epidemiology and Life Cycle A. caninum is a common hookworm of dogs and cats. It has worldwide distribution and is prevalent in the northern hemisphere. The parasite exists in areas with adequate sanitation, because dogs and cats indiscriminately defecate in yards, parks, and sandboxes. The life cycle of A. caninum is similar to that of A. duodenale, and the worm can be acquired orally; however, A. caninum does not fully mature in the human host, so no eggs are produced. Clinical Features and Pathophysiology A. caninum is a well-recognized cause of cutaneous larva migrans, a distinctive serpiginous rash caused by an abortive migration of the parasite in an unsupportive host. A. caninum also can cause eosinophilic enteritis, although not all eosinophilic enteritis is caused by this parasite (see Chapter 27). Patients with eosinophilic enteritis from A. caninum often are dog owners and present with colicky mid-abdominal pain and peripheral eosinophilia,[62] but they do not recall having cutaneous larva migrans. Intestinal biopsies show high numbers (>45/high-power field) of mucosal eosinophils,[63] and eosinophilic inflammation is most prevalent in distal small bowel. Unlike eosinophilic gastroenteritis, tissue eosinophilia is not present in the stomach. On endoscopy of the terminal ileum, patients might have scattered small superficial aphthous ulcers and mucosal hemorrhage.[64] Serologic evidence suggests that A. caninum also may be a cause of abdominal pain without eosinophilia or eosinophilic enteritis.[62]Diagnosis Diagnosis of A. caninum infestation is difficult. The parasite never fully matures, does not lay eggs, and is hard to detect. Serologic tests for A. caninum are research tools not routinely available. Therefore, treatment for A. caninum is empirical. Treatment Patients with distal small intestinal eosinophilic enteritis not attributable to another cause might benefit from empirical treatment for A. caninum. Albendazole 400 mg as a single oral dose or mebendazole 100 mg orally twice daily for three days is adequate to treat A. caninum infestation. Given for brief periods, these drugs are quite safe. WHIPWORM (TRICHURIS TRICHIURA) T. trichiura, commonly called whipworm, has worldwide distribution. People acquire Trichuris by ingesting embryonated parasite eggs. Most persons have no symptoms, although heavy infestations are associated with a dysentery-like syndrome. Treatment is mebendazole. Epidemiology An estimated 800 million people harbor T. trichiura. It occurs in temperate and tropical countries and remains prevalent in areas with suboptimal sanitation. In one equatorial Cameroon province, 97% of the school-age children had T. trichiura.[65] Whipworm eggs are sensitive to desiccation, so prevalence is low in desert climates. Life Cycle T. trichiura has a simple life cycle. Colonization occurs by ingesting the parasite egg, each of which contains one developed larva. The eggs hatch in the intestine, and larvae migrate to the cecum, where they mature, mate, and lay eggs. This process takes about eight to 12 weeks. Adult worms are approximately three centimeters long and have a thin tapered anterior region so that the worm resembles a whip (Fig. 110-9, Video 110-2).[66] A mature female worm lays about 20,000 eggs a day and can live for three years. Eggs are deposited with feces into the soil. Over the next two to six weeks, one larva develops within each egg, but the egg is not infective until it has fully embryonated. Therefore, T. trichiura does not multiply in the host and is not directly transmitted to other persons.
Clinical Features and Pathophysiology Most persons with T. trichiura infestation have no symptoms attributable to the parasite. Most people in an endemic area are colonized by small numbers (less than 15) of worms and for them, the parasite is a commensal organism rather than a pathogen. Some people harbor hundreds or even thousands of worms,[67] and they are the ones who develop symptoms[68]; this bimodal distribution of infestation persists after patients are treated and then become reinfected naturally, suggesting that unique host factors (genetic or behavioral) contribute to determining an individual patient's worm burden. Rectal prolapse can occur in children with extremely high numbers of T. trichiura worms.[69] Some persons with numerous worms have mucoid diarrhea and occasional bleeding, a combination of symptoms called the Trichuris dysentery syndrome (TDS). Children with this condition have growth retardation,[70] but studies attributing these symptoms to T. trichiura are complicated, because persons with TDS often are socioeconomically deprived and may be coinfected with other pathogens. Colonic biopsy specimens from children with TDS show few or no abnormalities compared with healthy local children,[71] other than an increase in mast cells[72] and in the number of cells that express TNF-α and calprotectin.[73] A different but closely related species, Trichuris muris, infests mice. Mouse strains that react to the parasite with a strong Th2 response, characterized by production of interleukin (IL)-4, IL-5, and IL-13, are able to expel the worms, whereas strains that respond with a Th1 response (interferon [IFN]-γ) have difficulty expelling the worms.[74] Blocking IL-4 makes resistant strains susceptible, and blocking IFN-γ makes susceptible strains resistant to chronic infestation with T. muris.[75] The type of immune response developed by inbred mice to T. muris is an important factor in determining length and intensity of infestation. A similar response in humans might explain why some people repeatedly acquire heavy infestations whereas others carry only a few worms. Diagnosis Diagnosis is made by identifying T. trichiura eggs in stool specimens. Trichuris eggs are 23 ?m by 50 ?m and have characteristic plugs at each end (see Fig. 110-3). Treatment T. trichiura is treated with mebendazole 100 mg twice a day for three days; alternatively, patients can take albendazole 400 mg each day for three days. Heavily infested patients might require seven days of treatment.[76] Single-dose treatment with albendazole is ineffective[27] but one treatment with a combination of albendazole (400 mg) and ivermectin (200 ?g/kg) appears quite effective, with cure rates of up to 80% and egg reduction rates of 94%.[77,78]PINWORM (ENTEROBIUS VERMICULARIS) E. vermicularis, commonly called pinworm, is the most common helminthic parasite encountered by primary care providers in developed nations. It is acquired by ingesting parasite eggs, and most people remain asymptomatic after being colonized. Diagnosis is made by the cellophane tape test. Treatment is mebendazole for the affected patient and for all family members. Epidemiology E. vermicularis is a quintessential intestinal parasite with no geographic constraints. It is transmissible by close contact with colonized persons. People have had pinworm for thousands of years, and before modern sanitation, colonization by pinworm probably was universal. E. vermicularis eggs were identified in a 10,000-year-old human coprolite found in Utah.[79] The pinworm Enterobius gregorii, originally thought to be a separate species of pinworm,[80,81] actually may be just a young adult form of E. vermicularis.[82] People of every socioeconomic group can acquire pinworm and it remains quite prevalent. School-age children are most often colonized, compelling other household members to acquire the parasite. Crowding and institutionalization promotes acquisition. Eggs can survive in the environment for approximately 15 to 20 days and are resistant to chlorinated water (e.g., swimming pools). Pinworm remains common in many areas, but it appears to be decreasing in prevalence. A survey of positive cellophane tape tests (see later) in New York City documented a sharp decline in positivity from 57 of 248 tests in 1971 to 17 of 165 in 1978 to 0 of 38 in 1986.[83] Similar trends are reported from California. Life Cycle E. vermicularis has a simple life cycle with a “hand to mouth” existence. The worm is acquired by ingesting parasite eggs. Most often these eggs are on the hands of the host; however, the small eggs also may become airborne, inhaled, and then swallowed. Eggs hatch in the duodenum, releasing larvae that molt twice as they mature and migrate to the cecum and ascending colon (Fig. 110-10, Video 110-3).[84] The parasites are small: adult males measure 0.2 mm by 2 to 5 mm, and adult females measure 0.5 mm by 8 to 13 mm. After mating, gravid females migrate to the rectum. During the night, egg-laden females migrate out of the anal canal and onto the perianal skin. Each female deposits up to 17,000 eggs, which mature rapidly, becoming infective within six hours. Pinworm infestation typically causes perianal itching, and scratching gathers eggs onto the hands, promoting reinfection and transmission to others.
Clinical Features and Pathophysiology E. vermicularis is an extremely well adapted parasite that produces no specific symptoms in the vast majority of colonized persons. Most symptoms are minor, such as pruritus ani and restless sleeping. Rarely, pinworm causes eosinophilia or eosinophilic enteritis.[85] Vulvovaginitis is more common in girls with pinworm than in girls without this infection. Vulvovaginitis may be caused by migration of the worms into the introitus and genital tract. Dead worms and eggs encased in granulomas have been found in the cervix, endometrium, fallopian tubes, and peritoneum, attesting to the migratory effort of female worms.[86] Ectopic enterobiasis is rare and causes no or very little overt pathology. Infestation with E. vermicularis can influence mucosal immune responses. One case report described a 12-year-old girl with pinworm and apparently latent ulcerative colitis, who developed severe ulcerative colitis after treatment with pyrantel to remove the worms.[87] While she was colonized with E. vermicularis, intestinal biopsies showed increased expression of mRNA for IL-4, transforming growth factor (TGF)-β, IL-10, and FOXP3 compared with biopsy specimens taken after anthelminthic treatment; these transcripts are associated with immune regulatory pathways that suppress inflammation. Diagnosis E. vermicularis eggs are not plentiful in stool, an observation that might explain the low prevalence rates found in studies that only use stool specimens for diagnosis. The NIH cellophane tape test is the classic diagnostic test for pinworm. A two- to three-inch piece of clear tape is applied serially to several perianal areas in the morning before washing. The tape is then applied to a glass slide. Microscopic evaluation demonstrates parasite eggs that measure 30 by 60 ?m, have a thin shell, and appear flattened on one side. Three to seven daily samples are needed to exclude pinworm infestation. Treatment Pinworm actually requires no treatment unless the patient is symptomatic. It is highly transmittable, however, and for that reason should be expunged. E. vermicularis is readily treated with a single 100-mg dose of mebendazole or a 400-mg dose of albendazole. Reinfestation is common, and patients should receive a second treatment after 15 days. All members of the family should be treated and clothes and bed linens should be washed. Albendazole and mebendazole are potentially teratogenic. Because E. vermicularis has very low pathogenicity, treatment of pregnant women should be postponed until after delivery. TRICHINELLA SPECIES Trichinosis is a systemic illness caused by any of the eight closely related Trichinella species. People acquire the parasite by ingesting larvae present in raw or undercooked meat such as pork. Trichinosis has both intestinal and systemic phases characterized sequentially by nausea and diarrhea, fever, myalgia, and periorbital edema. Intense exposure can cause death due to severe myositis, neuritis, and thrombosis. Treatment is albendazole and glucocorticoids. Epidemiology Trichinosis is acquired by eating raw or undercooked meat that contains parasite larvae of Trichinella species. Worldwide, domestic pigs are the most common carriers. Trichinella species are divided into two groups,[88] one that forms encapsulated muscle cysts and only infests mammals (Trichinella spiralis, Trichinella britovi, Trichinella nelsoni, Trichinella native, Trichinella murrelli), and one that does not form encapsulated cysts and infests mammals and birds (Trichinella pseudospiralis) or mammals and reptiles (Trichinella papuae, Trichinella zimbabwensis). To date only T. zimbabwensis has not been implicated in human disease. These species are closely related, morphologically nearly identical, and distinguished using molecular approaches. Trichinella has worldwide distribution, with T. nativa and T. murrelli in the Arctic and subarctic regions; T. spiralis and T. pseudospiralis in the Americas, Europe, and Russia; T. britovi in Europe, north Africa, the Middle East, and Asia; T. nelsoni in equatorial Africa; T. zimbabwensis in Zimbabwe, Ethiopia, and Mozambique; and T. papuae only in Papua New Guinea. Each of the Trichinella species can infest any mammal. T. nativa is resistant to freezing for up to five years. Trichinosis was much more common in the United States than it is now. In the late 1940s, about 400 cases per year of symptomatic trichinosis were reported to various health agencies, and this number dropped to an average of 14.4 cases per year in the time period 1997 to 2001[89]; reports from Germany show a similar pattern.[90] This decrease is explained by two major factors: First is the strong admonition to thoroughly cook all pork products; second is a change in farming practice to now feed pigs only grain. Industrialized pig farms in North America have been free of trichinosis for more than 50 years, but trichinosis is a reemerging illness in eastern Europe, related to relaxed enforcement of regulations.[91] Currently, most reported cases involve a discrete exposure. For example, a 1991 outbreak in Wisconsin involved 40 people who ate pork sausage from one shop. A 1995 outbreak in Idaho involved 10 people who ate cougar jerky.[92] A 2005 outbreak in Canada involved at least 14 people who ate frozen then stewed black bear meat.[93] In France, several outbreaks have resulted from eating raw horse meat.[94] This emphasizes that all mammals including herbivores can transmit Trichinella.Life Cycle The same host harbors both the adult and larval form of Trichinella.[95] People acquire the parasite by eating raw or undercooked meat that contains encapsulated parasite larvae. Each cyst dissolves in the digestive tract, releasing one larva that invades the small intestinal mucosa and lives within the cytoplasm of about 45 villus cells (Fig. 110-11). Larvae mature rapidly and mate within 30 hours. Adults are minute: Male worms measure 60 ?m by 1.2 mm and female worms measure 90 ?m by 2.2 mm. Females are viviparous and begin releasing larvae about one week after their initial ingestion. Adults are short-lived, producing larvae for only four weeks, by which time they are expelled by the host.
The larvae live much longer than the adult worms. Larvae measure six by 100 ?m and enter the intestinal blood and lymphatic vessels. They are distributed by the circulatory system through the body but develop only within striated muscle. The larva enters a striated muscle fiber but does not kill the myocyte. Instead, it induces the cell to transform into a novel nurse cell that houses and feeds the parasite. The larva grows and develops into the infective stage in about five weeks. The coiled larvae remain viable for many years awaiting ingestion by another animal. Clinical Features and Pathophysiology Although most infestations with Trichinella are asymptomatic, significant exposure produces illness and even death.[96] Clinical trichinosis has two phases caused by the enteral (adult) and parenteral (larval) stages of the parasite. Intestinal symptoms result from enteritis due to adult worms that have embedded themselves in the intestinal epithelium. Enteritis produces abdominal pain, nausea, vomiting, diarrhea, and low-grade fever. Intestinal symptoms begin about two days to one week and peak at two weeks after ingestion of contaminated meat. The timing and severity of symptoms vary with intensity of exposure. The intestinal phase of trichinosis often is misdiagnosed as viral gastroenteritis or food poisoning. T. spiralis also infests mice and rats, permitting detailed study of the intestinal phase of infection.[97] Mice begin to expel adult worms about two weeks after initial infestation. Type 2 (Th2) cytokines (IL-4 and IL-5) promote worm expulsion. Expulsion of adult worms results from focal immune attack, increased secretions, and enhanced intestinal motility; T lymphocytes, eosinophils, and mast cells assist this primary response. Rats previously exposed to T. spiralis rapidly expel the parasite upon rechallenge, a protection likely resulting from an immediate-type hypersensitivity response to the parasite triggered by IgE-armed mast cells. The parenteral phase of trichinosis begins with the birth of migratory larvae about one week after ingestion of the contaminated meat. Larvae migrate into muscle and other organs such as the brain, spinal cord, and heart, evoking inflammatory responses; high fever, myalgia, periorbital edema, dysphagia, headache, and paresthesia result. Symptoms peak about four to five weeks after initial exposure and can take months to resolve. The severity and timing of symptoms vary with the intensity of exposure. Many patients develop systemic complaints without prior intestinal symptoms. The inflammatory response to migrating larvae produces myositis. Patients have eosinophilia and an elevated serum level of creatine phosphokinase (CPK). An intense exposure can cause fatal myocarditis, neuritis, and vasculitis or thrombosis. Patients are at highest risk of death between the third and sixth week after exposure. Because trichinosis is rare, index cases often are misdiagnosed initially. Numerous persons presenting in a narrow time frame and with similar and compatible symptoms should prompt consideration of trichinosis as the diagnosis. Diagnosis Trichinella cannot by diagnosed by stool examination or intestinal biopsy. Trichinella species do not lay eggs, and no larvae are present in stool specimens. Even with heavy infestations, adult worms are too uncommon to be found by random biopsy. Diagnosis is made by muscle biopsy demonstrating larvae within nurse cells. Diagnosis also can be made by serology. Acute and convalescent serum samples confirm a rise in anti-Trichinella antibody. Treatment Although adults are short-lived, treatment with albendazole 400 mg twice a day or mebendazole 5 mg/kg/day for 10 to 15 days[98] is warranted and abbreviates the production of larvae by adult worms. Addition of glucocorticoids reduces inflammation and systemic symptoms; however, glucocorticoids given in the absence of a benzimidazole can prolong the intestinal phase, increasing the number of larvae released. ANISAKIS SIMPLEX A. simplex and another anisakid, Pseudoterranova decipiens, can infect people transiently, causing abdominal pain, hematemesis, or intestinal inflammation. A. simplex is also a potent allergen that might explain some cases of fish allergy. Anisakidosis is acquired by eating raw or undercooked fish. No treatment is usually required. Epidemiology and Life Cycle A. simplex and P. decipiens infest fish and marine mammals.[99] People become accidental hosts by eating raw or pickled fish. Anisakidosis has become more common with the increased popularity of eating raw fish (e.g., sushi). Many species of saltwater fish harbor A. simplex larvae including herring, mackerel, salmon, plaice, and squid. The parasite larvae initially infest crustaceans that are consumed by fish. The larvae migrate to the fish musculature and, if a parasitized fish is eaten by another fish, the larvae again migrate to the musculature of their new host. Eventually, a parasitized fish is eaten by a marine mammal that serves as the definitive host. In the marine mammal, the parasite larvae mature into adult intestinal worms and lay eggs that are passed with feces, the eggs hatch to release larvae that infest crustaceans, and the life cycle is thus renewed. Clinical Features and Pathophysiology A. simplex and P. decipiens cause transient infestations in humans. They do not reach full maturity in humans and therefore produce no eggs. The most common gastrointestinal symptom is acute severe stomach pain with nausea and hematemesis shortly after eating larva-infested raw fish. Endoscopy may demonstrate a small larva partially penetrating the gastric or intestinal wall.[100,101] Rarely, A. simplex can enter the intestinal wall and cause a strong inflammatory reaction that can mimic acute appendicitis[102] or Crohn's disease. Human infestations with either A. simplex or P. decipiens is termed anisakidosis after the family name (Anisakidae) for these parasites. A. simplex is a potent allergen, and many cases of seafood (fish) allergy actually may be reactions to A. simplex,[103] including anaphylaxis from well-cooked marine fish.[99,104] In Spain, 12% to 22% of persons are seropositive for IgE against A. simplex.[105,106]Diagnosis and Treatment A history of recent (within three days) ingestion of raw fish suggests anisakidosis in the appropriately symptomatic patient. Diagnosis is made by finding the larvae on endoscopy or in surgically excised specimens. Gastric anisakidosis is diagnosed by endoscopy, and endoscopic removal of the anisakid alleviates symptoms. Intestinal anisakidosis can prompt surgery for patients presenting with symptoms of acute small bowel obstruction or peritonitis,[107] but surgery may be avoidable if a recent history of eating raw fish is elicited and conservative treatment is tolerated.[108] A. simplex and P. decipiens infestations are transient because the parasites do not survive in humans. Therefore, treatment with an anthelminthic is not needed.
Parasitic worms are found worldwide. Modern travel, emigration,[1] and consumption of “exotic” cuisines allow intestinal helminths to appear in any locale. People now acquire tropical helminths without leaving their industrialized temperate cities. Travel history is a critical, but often overlooked, aspect of the patient interview. Many helminths survive for decades within a host, so even a remote history of visits to or emigration from countries where they are endemic is important. Fresh food is flown around the world and often consumed raw.
Physicians need to remain alert to the possibility of infection with these organisms because some cause severe disease that requires years to develop or occurs only under special circumstances. For example, patients might have occult Strongyloides stercoralis until treatment with glucocorticoids causes fulminant disease, occult Clonorchis sinensis until they develop cholangiocarcinoma, or occult Schistosoma mansoni until they develop portal hypertension and bleeding from esophageal varices.
In developed countries, we usually diagnose an intestinal helminth because we stumble across it rather than because we actively pursue it. Helminths are complex organisms well adapted to their hosts; like quiet house guests, most cause no symptoms. Worms rarely cause diarrhea, but many medical laboratories do not assay formed stool routinely for parasite eggs. Physicians need to communicate their concerns of possible helminthic infection to laboratory personnel. A telephone call to the local laboratory before a sample is sent can improve diagnostic results dramatically. Occasionally, alarmed patients bring proglottids or whole worms that they passed with their stools. These specimens should be fixed in 5% aqueous formalin and sent for identification.[2] All specimens should be handled carefully with full precautions to avoid accidental exposure. Some helminthic infections are difficult to diagnose, especially when the worm burden is light. Diagnosis can require serologic evaluation, analysis of multiple stools, or use of concentration techniques in addition to a high level of physician awareness. For example, S. stercoralis eggs do not appear in the stool, and diagnosis is best made serologically. Ancyclostoma caninum causes eosinophilic enteritis but does not lay eggs when infecting people. Some helminths can cause severe disease, but this is unusual. Most persons colonized with helminths have no symptoms or illness attributable to the parasites. Only with heavy infections does disease result. Well-adapted worms usually act more as commensals than as pathogens. It is even possible that exposure to helminths affords some protection against disease due to excessive immune reactions.[3,4] Helminths induce immune regulatory pathways.[5] Recent studies in mice and rats show that exposure to helminths can be used to prevent or treat colitis,[3,6-8] insulin-dependent diabetes,[9] and autoimmune encephalitis.[10,11] Studies in humans show that helminth exposure improves ulcerative colitis[12] and probably Crohn's disease[13,14] and that helminth eradication increases atopy.[15] Although it remains important to treat helminthic infections when they are discovered, further research on these organisms can enable discovery of new approaches to treat immune-mediated disease. This chapter is divided into three sections: nematodes (roundworms), cestodes (tapeworms), and trematodes (flukes or flatworms). For the most part, each worm is addressed separately, noting its epidemiology, life cycle, clinical manifestations, diagnosis, and treatment. NEMATODES ASCARIS LUMBRICOIDES Ascaris lumbricoides is the largest of the nematode parasites that colonize humans. Females can grow to 49 cm (19 inches).[16] The name “lumbricoides” alludes to its resemblance to earth worms (Lumbricus sp.). The parasite is acquired by ingesting its eggs. Ascaris can cause intestinal obstruction and pancreaticobiliary symptoms. Treatment is albendazole. Epidemiology A. lumbricoides has a worldwide distribution, although these parasites are most numerous in less-developed countries and in areas with poor sanitation. About 25% of the world's population (1.2 billion people) harbor A. lumbricoides.[17,18] Children acquire the parasite by playing in dirt contaminated with eggs, whereas adults most often are infected by farming or eating raw vegetables from plants fertilized with untreated sewage. Pigs harbor Ascaris suum, which is closely related to A. lumbricoides, but cross-infection is rare.[19]Life Cycle Humans acquire the parasite by ingesting embryonated eggs that contain third-stage larvae. Freshly deposited fertilized eggs incubate in the soil for 10 to 15 days while the embryo develops and molts twice. The eggs become infective after this incubation period. The eggs are remarkably stable, can survive freezing, and can remain viable for seven to 10 years. The eggs are resistant to most chemical treatments including pickling, but they rapidly die in boiling water. Once ingested, eggs hatch in the duodenum and release their larvae, which penetrate the intestinal wall and enter the mesenteric venules and lymphatics. Larvae migrating with portal blood pass to the liver, through the sinusoids to the hepatic veins, and then through the right side of the heart to enter the lungs. Larvae migrating via the lymphatics pass through mesenteric lymph nodes to the thoracic duct and enter the superior vena cava to arrive in the lungs. The larvae then lodge in the pulmonary capillaries and break into the alveoli, where they molt twice while growing to 1.5 mm in length. Larvae then ascend the tracheobronchial tree, and arrive in the hypopharynx, they are again swallowed, and pass into the small intestine, where they molt again and finally mature. Mature male A. lumbricoides are smaller (10 to 30 cm) than females (20 to 49 cm). Worms mate in the small intestine and females deposit about 200,000 eggs a day. Adult worms live for about one year (six to 18 months). Because their eggs require incubation in the soil to become infective, Ascaris does not multiply in the host. Continued infestation requires repeat ingestion of embryonated eggs. Clinical Features and Pathophysiology A. lumbricoides produces no symptoms in most infected persons. Often, worms are found unexpectedly on endoscopy[20,21] (Video 110-1) or are seen on radiologic imaging,[22] or eggs are identified in stool specimens of patients with symptoms not directly attributable to the worms. Disease usually develops only in those with heavy worm burdens: pulmonary, intestinal, and hepatobiliary ascariasis are well described. Pulmonary ascariasis (Ascaris pneumonia) develops four to 16 days after ingesting infective eggs. The larvae migrate into the alveoli and elicit an inflammatory response that can cause consolidation. The pneumonia usually is self-limited but can be life-threatening. Large numbers of mature worms can cause severe intestinal symptoms including abdominal pain, distention, nausea, and vomiting. The most common complication of intestinal ascariasis is partial or complete small bowel obstruction; such patients often have a history of passing mature worms in their stool or vomitus. Patients with intestinal obstruction generally have more than 60 worms,[23] and the rare patients with fatal cases often have more than 600 worms. Fatality results from intestinal necrosis caused by obstruction, intussusception, or volvulus (Fig. 110-1).[24] Most cases of obstruction, absent signs of peritonitis or perforation, can be managed conservatively.
| Figure 110-1. Small intestinal obstruction caused by Ascaris lumbricoides. (From Wasadikar PP, Kulkarni AB. Intestinal obstruction due to ascariasis. Br J Surg 1997; 84:410.) |  |
A. lumbricoides are highly motile. Mature worms can enter the ampulla of Vater (Fig. 110-2) and migrate into the bile or pancreatic ducts, causing biliary colic, obstructive jaundice, ascending cholangitis, acalculous cholecystitis, or acute pancreatitis.[16] Pregnancy can promote biliary trespass.[25] The worms can move in and out of the papilla, producing intermittent symptoms and fluctuating laboratory tests. Recurrent ascending cholangitis or acute pancreatitis from ascariasis is rare in highly developed Western countries but can be fatal if the diagnosis is not entertained.[26]
 | |
| Figure 110-2. A, Endoscopic view of Ascaris lumbricoides partially within the ampulla of Vater. B, Ascaris lumbricoides removed. (From Esser-Kochling BG, Hirsch FW. Images in clinical medicine. Ascaris lumbricoides blocking the common bile duct. N Engl J Med 2005; 352:e4.) | |
Diagnosis Often it is an alarmed patient who discovers Ascaris after passing a motile adult worm with a bowel movement. The worms, however, usually do not cause diarrhea. Most patients do not have specific symptoms or eosinophilia. Ascaris eggs are visible in direct smears of stool (Fig. 110-3). The eggs begin to appear in the stool about two months after initial exposure. Fertilized eggs are 35 by 55 ?m and have a thick shell and outer layer; females also lay unfertilized eggs that are larger (90 by 44 ?m) and have a thin shell and outer layer. Ascaris eggs that lose their outer layer resemble the eggs of hookworms.
 | |
| Figure 110-3. Stool specimen containing helminth eggs. A, Ascaris lumbricoides. B, Hookworm. C, Trichuris trichiura. D, Fasciolopsis buski. (A to D, Courtesy of Mae Melvin, MD, Atlanta, Ga.) | |
Adults worms may be seen at endoscopy,[21] or identified on upper gastrointestinal series as long, linear, filling defects within the small intestine.[22] The worms retain barium after it has cleared from the patient's gastrointestinal tract, producing linear opacities. Similar findings are seen on endoscopic retrograde cholangiopancreatography (ERCP) if a worm is in the bile or pancreatic duct (Fig. 110-4). Ascaris also has a characteristic appearance on ultrasound examination of the biliary tree or pancreas: They appear as long, linear echogenic strips that do not cast acoustic shadows.[22]
 | |
| Figure 110-4. Endoscopic retrograde cholangiogram showing several Ascaris lumbricoides in the bile duct. (From van den Bogaerde JB, Jordaan M. Intraductal administration of albendazole for biliary ascariasis. Am J Gastroenterol 1997; 92:1531.) | |
Treatment Asymptomatic colonization with A. lumbricoides is treated easily with a single 400-mg oral dose of albendazole. Albendazole inhibits glucose uptake and microtubule formation, effectively paralyzing the worms. Albendazole is poorly absorbed but is teratogenic, and therefore it should not be used in pregnant women. When possible, treatment with this agent should be delayed until after delivery. Single-dose mebendazole also is efficacious for Ascaris.[27] A study of 1042 pregnant women in Peru found no adverse effect of a single 500-mg oral dose of mebendazole on birth outcomes.[28] Patients with pulmonary ascariasis should be treated with glucocorticoids to reduce the pneumonitis and be given two 400-mg doses of albendazole one month apart. Because albendazole is poorly absorbed, ascaricidal tissue concentrations are not achieved. The first dose kills mature worms that finished migrating to the intestine, and the second dose kills worms that were in transit when the first dose was given. Albendazole can cause nausea, vomiting, and abdominal pain. Intestinal ascariasis with obstruction often can be treated conservatively with fluid resuscitation, nasogastric decompression, antibiotics, and one dose of albendazole. Surgery is not required unless the patient develops signs of volvulus, intussusception, or peritonitis. If the bowel is viable, an enterotomy allows intraoperative removal of worms. Albendazole may be held until after the obstruction resolves and then used to eradicate any remaining organisms. Hepatobiliary ascariasis also can be treated conservatively with fluid resuscitation, bowel rest, and antibiotics.[29] Worms in the bile duct are not effectively treated with albendazole because it is poorly absorbed and not concentrated in the bile. This feature of albendazole is advantageous because were paralyzed worms unable to pass through the sphincter of Oddi, they could become trapped in the bile duct. Patients with hepatobiliary ascariasis should be treated with albendazole each day for several days because the worms only become susceptible when they migrate out of the bile duct. Worms also can invade the pancreatic duct and can be treated conservatively, as for hepatobiliary ascariasis.[30] Ascending cholangitis, acute obstructive jaundice, or acute pancreatitis requires emergent ERCP with worm extraction from the ducts by balloon, basket, or forceps—preferably without sphincterotomy. Ampullary sphincterotomy permits worms easier access to the ducts and can increase the risk of recurrent pancreaticobiliary ascariasis.[31]STRONGYLOIDES STERCORALIS S. stercoralis is a free-living tropical and semitropical soil helminth, the filariform larvae of which can penetrate intact skin. As a parasite, Strongyloides lives in the intestine and lays eggs that hatch while still in the bowel. Filariform larvae develop within the intestine, migrate along defined paths, and mature to increase the number of adult parasites in the host. Immunosuppression and glucocorticoid treatment cause a fulminant reproduction of parasites that can prove fatal. Treatment is ivermectin. Epidemiology S. stercoralis is endemic in tropical and semitropical regions, but it can also be acquired in rural southeastern United States and northern Italy. Strongyloides exists as a free-living organism that does not require a host to replicate. Improved sanitation does not remove the risk of acquiring the parasite from soil. Patients from endemic areas, military veterans who served in Asia, and prisoners of war are at high risk for subclinical strongyloidiasis. Life Cycle Adult male and female S. stercoralis live in the soil and lay eggs that hatch rhabditiform larvae. Rhabditiform larvae develop in the soil into mature adults to complete the life cycle of this worm. Rhabditiform larvae (250 ?m) also can develop into longer (500 ?m) infective filariform larvae that can penetrate any area of skin contacting soil, after which they migrate through the dermis to enter the vasculature. The larvae circulate with the venous blood until they reach the lungs, where they break into the alveoli and ascend the bronchial tree. The worms then are swallowed with bronchial secretions and pass into the small intestine, where they embed in the jejunal mucosa and mature. Female S. stercoralis can lay fertile eggs by parthenogenesis and therefore do not require males to reproduce. The eggs hatch within the small intestine, and rhabditiform larvae migrate into the lumen. Rhabditiform larvae, not eggs, are passed in the stool. A critical feature of S. stercoralis infestation is that some rhabditiform larvae sporadically develop into infective filariform larvae within the intestine. Filariform larvae are able to reinfest (autoinfect) the patient, thereby increasing the parasite burden and permitting prolonged colonization so that subclinical strongyloidiasis can exist for many decades after the host has left an endemic area. Clinical Features and Pathophysiology Most patients with S. stercoralis have no abdominal symptoms. Patients might have a serpiginous urticarial rash (larva currens) caused by the rapid (5 to 10 cm/hour) dermal migration of filariform larvae. This rash often occurs on the buttocks from larvae entering the perianal skin after they exit the anus during autoinfection. A study of prisoners of war found this creeping eruption to be a far more common symptom of chronic strongyloidiasis than were gastrointestinal complaints.[32] Occasionally, patients have nausea, abdominal pain, or unexplained occult gastrointestinal blood loss from S. stercoralis. The parasite also can cause colonic inflammation that resembles ulcerative colitis but is more right-sided and strongly eosinophilic.[33-35] While the parasite burden remains balanced, symptoms are minimal or absent. Immunosuppression or glucocorticoid administration upsets this balance. Previously asymptomatic, but chronically infested, patients develop fulminant, potentially fatal strongyloidiasis due to massive autoinfection.[36,37] The mechanisms that permit massive autoinfection are unknown, but events that inhibit Th2-directed immune responses can release eosinophil-mediated control of the parasites. In addition, glucocorticoids can act directly on the parasites to increase the development of infective filariform larvae.[38] Fulminant disseminated strongyloidiasis rarely complicates HIV and AIDS.[39] Massive autoinfection produces disseminated fulminant strongyloidiasis. Migrating filariform larvae injure the intestinal mucosa and carry luminal bacteria into the bloodstream, resulting in polymicrobial sepsis with enteric organisms. Streptococcus bovis endocarditis or meningitis[40] also can result. Numerous larvae migrating through the lungs cause pneumonitis, and worms can arrive in unusual locations such as the brain. Fulminant strongyloidiasis often is fatal. Diagnosis A recent survey of United States physicians-in-training demonstrated very poor ability to identify or even consider strongyloidiasis.[41] Patients with chronic strongyloidiasis often are asymptomatic. Peripheral blood eosinophils may be elevated, but a normal eosinophil count does not argue against infestation with the parasite. Currently, the best method for detecting exposure is enzyme-linked immunosorbent assay (ELISA) for immunoglobulin (Ig) G antibodies against S. stercoralis. This assay is performed by the Centers for Disease Control and Prevention (CDC) in the United States and is 95% sensitive,[42] sensitivity being highest for immigrants with prolonged exposure and lowest for returning visitors with lower-level recently acquired infestation.[43] False-positive reactions can occur in patients exposed to other helminthic parasites,[44] and serologic positivity can indicate prior exposure to S. stercoralis, not necessarily active infestation. Because chronic strongyloidiasis can remain subclinical and difficult to detect for decades, however, treatment of seropositive patients is warranted. Indeed, some argue that patients with only suspected strongyloidiasis, such as immigrants from endemic countries who have elevated eosinophil counts, should be treated empirically before glucocorticoid therapy.[45] Active infestation can be diagnosed by finding rhabditiform larvae in direct smears of the stool, though this is an insensitive method. A 10-fold more sensitive technique is to spread stool on an agar plate and look for serpentine tracks left by migrating larvae.[46] Intestinal biopsy is also an insensitive means of diagnosis. Treatment Chronic strongyloidiasis is best treated with one dose of ivermectin (200 ?g/kg) given orally; this dose is used in both adult and pediatric patients. Ivermectin is better tolerated than thiabendazole. Ivermectin paralyzes the intestinal adult worms but not the larvae migrating through tissue, and therefore patients can develop recurrent infestation from migrating larvae; a repeat dose after two weeks helps to prevent this outcome. Successful treatment causes a fall in antibody titer by six months in most (about 90%) patients.[42] Immunocompromised patients require repeat doses given 2, 15, and 16 days after the first dose.[37]CAPILLARIA (PARACAPILLARIA) PHILIPPINENSIS Capillariasis is acquired by eating raw fish that are infested with the parasite.[47] The nematode causing capillariasis has been renamed from Capillaria philippinensis to Paracapillaria philippinensis,[48] but by any name, it is deadly. The parasite replicates in the host, producing an ever-increasing number of intestinal worms. Patients develop protein-losing, sprue-like diarrhea with progressive emaciation and anasarca, which ultimately leads to death. Treatment is albendazole. Epidemiology The first known human case of capillariasis was reported in 1964. It remains a rare but deadly parasitic infestation. From 1965 through 1968, an epidemic in the rural Philippines involved 229 cases, with an overall mortality rate of 30%.[49] As the name implies, Paracapillaria phillippinensis is endemic to the Philippines, but it also is endemic in Thailand and cases occur in Japan, Taiwan, Egypt, and Iran. Modern travel transports cases worldwide.[50]Life Cycle Birds, not humans, are the natural hosts for P. philippinensis. In the avian small intestine, the larvae mature into adults. The adults are very small, measuring up to 3.9 mm for males and 5.3 mm for females. Adult worms mate and produce eggs. Eggs are deposited in bird droppings into ponds and rivers and are swallowed by fish to complete the life cycle. People become infested with the worm by eating raw or undercooked freshwater or brackish-water fish that contain the parasitic larvae. Some female adult P. philippinensis are larviparous, producing infective larvae instead of eggs. These larvae then mature in the small intestine and increase the parasite burden. This pathway of autoinfection permits a massive increase in parasite numbers. A rhesus monkey originally fed 27 larvae had more than 30,000 worms by 162 days of infection.[51]Clinical Features and Pathophysiology Capillariasis produces a progressive sprue-like illness. Symptoms begin with vague abdominal pain and borborygmi. Two or three weeks after infection, patients begin to have diarrhea. Initially intermittent, diarrhea becomes persistent and increasingly voluminous. Patients rapidly waste from escalating steatorrhea and protein-losing enteropathy. Eventually they manifest emaciation, anasarca, and hypotension; diarrhea produces severe hypokalemia. If untreated, patients die from cardiac failure or secondary bacterial sepsis usually about two months after the initial onset of symptoms. The progressive disease is believed to result from an ever-increasing number of poorly adapted intestinal parasites. In autopsy studies, the jejunal intestinal mucosa showed flattened, denuded villi with numerous plasma cells, lymphocytes, macrophages, and neutrophils infiltrating the lamina propria.[47]Diagnosis Diagnosis is made by finding eggs and larvae in stool specimens. No serologic tests for capillariasis are available. Symptomatic patients have detectable eggs in their stool. The eggs are easily confused with those of Trichuris trichiura, but T. trichiura eggs have prominent bipolar plugs that appear cut off in P. phillipinensis.[47]Treatment Capillariasis requires extended anthelminthic treatment with albendazole 200 mg orally twice daily for 10 days or mebendazole 200 mg orally twice daily for 20 days to prevent recurrence. Albendazole is better tolerated than mebendazole, which can cause headache, diarrhea, and abdominal pain. Extended treatment is necessary because larvae are resistant to these agents. HOOKWORMS (NECATOR AMERICANUS, ANCYLOSTOMA DUODENALE, AND ANCYLOSTOMA CANINUM) Worldwide, an estimated 740 million people are infested with hookworm,[17] usually by Necator americanus, Ancylostoma duodenale, or a mixture of the two. Hookworm is acquired by skin contact with contaminated soil. Moderate infestation contributes to iron deficiency. Hookworm should be suspected in patients with eosinophilia and iron-deficiency anemia. The dog and cat parasite Ancylostoma caninum is a cause of eosinophilic enteritis. Treatment is albendazole. Necator americanus and Ancylostoma duodenale Epidemiology The geographic distribution of N. americanus and A. duodenale extensively overlap, but N. americanus predominates in the Americas, South Pacific, Indonesia, southern India, and central Africa, whereas A. duodenale is more common in North Africa, the Middle East, Europe, Pakistan, and northern India. Hookworm infestation is acquired by contacting soil contaminated with human waste. Hookworm is endemic in tropical to warm temperate areas that lack sufficient sewage facilities. Indigenous hookworm infestation largely has been eradicated in the United States, although small pockets of transmission still exist. Life Cycle Infective third-stage hookworm larvae penetrate intact skin, such as between the toes of bare feet while walking on contaminated ground. Larvae migrate through the dermis to reach blood vessels. This migration can cause a pruritic, serpiginous rash, cutaneous larva migrans (Fig. 110-5). Ancylostoma braziliense normally infests dogs and cats, but it produces a similar rash during infective dermal wandering in humans and is the usual cause of cutaneous larva migrans. Larvae of N. americanus and A. duodenale enter blood vessels in the skin and migrate with venous flow through the right side of the heart to the lungs. A. duodenale larvae can arrest their migration and become dormant for many months before proceeding to the lungs.[52] In the lungs, larvae penetrate the alveoli and enter the air spaces, after which they migrate up the pulmonary tree, are swallowed with saliva, and pass into the small intestine, where they mature. Patients also can acquire A. duodenale by directly ingesting larvae crawling on contaminated fresh vegetables. Adult worms develop large buccal cavities and graze on the intestinal mucosa, ingesting epithelial cells and blood (Figs. 110-6 and 110-7). Adults are about one centimeter long and can live for up to 14 years. Mature worms mate and lay eggs. Each female N. americanus lays about 10,000 eggs a day, and each female A. duodenale lays about 20,000 eggs a day. Eggs are deposited with feces in moist, shady soil, where they hatch to release larvae. The larvae molt twice after which they move to the soil surface and seek a suitable host.
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| Figure 110-5. Serpiginous rash caused by hookworm larvae migrating through the dermis. (Courtesy of the University of Iowa Department of Dermatology, Iowa City, Ia.) | |
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| Figure 110-6. Scanning electron micrographic view of the buccal cavities of Ancylostoma duodenale (left) and Necator americanus (right). (From Hotez PJ, Pritchard DI. Hookworm infection. Sci Am 1995; 272:70.) | |
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| Figure 110-7. Longitudinal section of a hookworm grazing on intestinal mucosa. (Courtesy of Wayne M. Meyers, Washington, DC.) | |
Clinical Features and Pathophysiology Light infestations with N. americanus and A. duodenale cause no symptoms.[53] The major consequence of moderate and heavy hookworm infestation is iron deficiency. Adult worms feed on intestinal epithelial cells and blood. The closely related A. caninum (see later) secretes anticoagulant peptides that inhibit clotting factors[54] and platelet aggregation,[55] thereby preventing hemostasis and permitting the hematophagous parasites to feed on host blood. Intestinal blood loss is estimated to be 0.01 to 0.04 mL/day per adult N. americanus and 0.05 to 0.3 mL/day per adult A. duodenale.[56] With a moderate number of worms, this blood loss becomes appreciable (Table 110-1). Iron deficiency results when iron loss outstrips iron absorption. The average North American diet is high in iron so anemia might not develop, and men with a diet high in iron (more than 20 mg/day) can tolerate up to 800 adult hookworms without developing anemia.
Table 110-1 -- A Comparison of Daily Physiologic Iron Losses and Iron Losses Due to Hookworm Infection in Women*
| CONDITION | IRON LOSS (MG/DAY) |
|---|---|
| Physiologic Losses | |
| Menstruation | 0.44 |
| Pregnancy | 2.14 |
| Lactation | 0.23 |
| Losses Due to Hookworm Infection | |
| Necator americanus (60-200 worms) | 1.10 |
| Ancylostoma duodenale (20-100 worms) | 2.30 |
Adapted from Stoltzfuss RJ, Dreyfuss ML, Chwaya HM, Albonico M. Hookworm control as a strategy to prevent iron deficiency. Nutr Rev 1997; 55:223-32.
Infestation with hookworm can modulate immune responses.[57] Clinical trials are under way to determine if subclinical infestation with hookworm inhibits immune-mediated disease such as Crohn's disease and asthma.[58,59] Dose-ranging studies on healthy volunteers suggested that low-level hookworm infestation (10 larvae) is well tolerated.[58]Diagnosis Hookworms can be visible endoscopically (Fig. 110-8),[60] but diagnosis is made by identifying eggs on direct smears of formalin-fixed stool (see Fig. 110-3). Evaluation of three stool specimens obtained on separate days should permit diagnosis of hookworm,[61] but light infestations can require concentration techniques. Eggs mature rapidly at room temperature and can hatch to release larvae. It is difficult to distinguish N. americanus eggs from those of A. duodenale simply by morphology.
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| Figure 110-8. Endoscopic view of Necator americanus in the duodenum (arrow). (From Reddy SC, Vega KJ. Endoscopic diagnosis of chronic severe upper GI bleeding due to helminthic infection. Gastrointest Endosc 2008; 67:990.) | |
Treatment Albendazole 400 mg given orally as a single dose is adequate treatment for hookworm. Mebendazole 100 mg given orally twice daily for three days also is effective but not as well tolerated. A. duodenale larvae can remain in a dormant state for months before maturing and causing relapse, a situation that is treated with a repeat course of albendazole or mebendazole. Ancylostoma caninum Epidemiology and Life Cycle A. caninum is a common hookworm of dogs and cats. It has worldwide distribution and is prevalent in the northern hemisphere. The parasite exists in areas with adequate sanitation, because dogs and cats indiscriminately defecate in yards, parks, and sandboxes. The life cycle of A. caninum is similar to that of A. duodenale, and the worm can be acquired orally; however, A. caninum does not fully mature in the human host, so no eggs are produced. Clinical Features and Pathophysiology A. caninum is a well-recognized cause of cutaneous larva migrans, a distinctive serpiginous rash caused by an abortive migration of the parasite in an unsupportive host. A. caninum also can cause eosinophilic enteritis, although not all eosinophilic enteritis is caused by this parasite (see Chapter 27). Patients with eosinophilic enteritis from A. caninum often are dog owners and present with colicky mid-abdominal pain and peripheral eosinophilia,[62] but they do not recall having cutaneous larva migrans. Intestinal biopsies show high numbers (>45/high-power field) of mucosal eosinophils,[63] and eosinophilic inflammation is most prevalent in distal small bowel. Unlike eosinophilic gastroenteritis, tissue eosinophilia is not present in the stomach. On endoscopy of the terminal ileum, patients might have scattered small superficial aphthous ulcers and mucosal hemorrhage.[64] Serologic evidence suggests that A. caninum also may be a cause of abdominal pain without eosinophilia or eosinophilic enteritis.[62]Diagnosis Diagnosis of A. caninum infestation is difficult. The parasite never fully matures, does not lay eggs, and is hard to detect. Serologic tests for A. caninum are research tools not routinely available. Therefore, treatment for A. caninum is empirical. Treatment Patients with distal small intestinal eosinophilic enteritis not attributable to another cause might benefit from empirical treatment for A. caninum. Albendazole 400 mg as a single oral dose or mebendazole 100 mg orally twice daily for three days is adequate to treat A. caninum infestation. Given for brief periods, these drugs are quite safe. WHIPWORM (TRICHURIS TRICHIURA) T. trichiura, commonly called whipworm, has worldwide distribution. People acquire Trichuris by ingesting embryonated parasite eggs. Most persons have no symptoms, although heavy infestations are associated with a dysentery-like syndrome. Treatment is mebendazole. Epidemiology An estimated 800 million people harbor T. trichiura. It occurs in temperate and tropical countries and remains prevalent in areas with suboptimal sanitation. In one equatorial Cameroon province, 97% of the school-age children had T. trichiura.[65] Whipworm eggs are sensitive to desiccation, so prevalence is low in desert climates. Life Cycle T. trichiura has a simple life cycle. Colonization occurs by ingesting the parasite egg, each of which contains one developed larva. The eggs hatch in the intestine, and larvae migrate to the cecum, where they mature, mate, and lay eggs. This process takes about eight to 12 weeks. Adult worms are approximately three centimeters long and have a thin tapered anterior region so that the worm resembles a whip (Fig. 110-9, Video 110-2).[66] A mature female worm lays about 20,000 eggs a day and can live for three years. Eggs are deposited with feces into the soil. Over the next two to six weeks, one larva develops within each egg, but the egg is not infective until it has fully embryonated. Therefore, T. trichiura does not multiply in the host and is not directly transmitted to other persons.
Clinical Features and Pathophysiology Most persons with T. trichiura infestation have no symptoms attributable to the parasite. Most people in an endemic area are colonized by small numbers (less than 15) of worms and for them, the parasite is a commensal organism rather than a pathogen. Some people harbor hundreds or even thousands of worms,[67] and they are the ones who develop symptoms[68]; this bimodal distribution of infestation persists after patients are treated and then become reinfected naturally, suggesting that unique host factors (genetic or behavioral) contribute to determining an individual patient's worm burden. Rectal prolapse can occur in children with extremely high numbers of T. trichiura worms.[69] Some persons with numerous worms have mucoid diarrhea and occasional bleeding, a combination of symptoms called the Trichuris dysentery syndrome (TDS). Children with this condition have growth retardation,[70] but studies attributing these symptoms to T. trichiura are complicated, because persons with TDS often are socioeconomically deprived and may be coinfected with other pathogens. Colonic biopsy specimens from children with TDS show few or no abnormalities compared with healthy local children,[71] other than an increase in mast cells[72] and in the number of cells that express TNF-α and calprotectin.[73] A different but closely related species, Trichuris muris, infests mice. Mouse strains that react to the parasite with a strong Th2 response, characterized by production of interleukin (IL)-4, IL-5, and IL-13, are able to expel the worms, whereas strains that respond with a Th1 response (interferon [IFN]-γ) have difficulty expelling the worms.[74] Blocking IL-4 makes resistant strains susceptible, and blocking IFN-γ makes susceptible strains resistant to chronic infestation with T. muris.[75] The type of immune response developed by inbred mice to T. muris is an important factor in determining length and intensity of infestation. A similar response in humans might explain why some people repeatedly acquire heavy infestations whereas others carry only a few worms. Diagnosis Diagnosis is made by identifying T. trichiura eggs in stool specimens. Trichuris eggs are 23 ?m by 50 ?m and have characteristic plugs at each end (see Fig. 110-3). Treatment T. trichiura is treated with mebendazole 100 mg twice a day for three days; alternatively, patients can take albendazole 400 mg each day for three days. Heavily infested patients might require seven days of treatment.[76] Single-dose treatment with albendazole is ineffective[27] but one treatment with a combination of albendazole (400 mg) and ivermectin (200 ?g/kg) appears quite effective, with cure rates of up to 80% and egg reduction rates of 94%.[77,78]PINWORM (ENTEROBIUS VERMICULARIS) E. vermicularis, commonly called pinworm, is the most common helminthic parasite encountered by primary care providers in developed nations. It is acquired by ingesting parasite eggs, and most people remain asymptomatic after being colonized. Diagnosis is made by the cellophane tape test. Treatment is mebendazole for the affected patient and for all family members. Epidemiology E. vermicularis is a quintessential intestinal parasite with no geographic constraints. It is transmissible by close contact with colonized persons. People have had pinworm for thousands of years, and before modern sanitation, colonization by pinworm probably was universal. E. vermicularis eggs were identified in a 10,000-year-old human coprolite found in Utah.[79] The pinworm Enterobius gregorii, originally thought to be a separate species of pinworm,[80,81] actually may be just a young adult form of E. vermicularis.[82] People of every socioeconomic group can acquire pinworm and it remains quite prevalent. School-age children are most often colonized, compelling other household members to acquire the parasite. Crowding and institutionalization promotes acquisition. Eggs can survive in the environment for approximately 15 to 20 days and are resistant to chlorinated water (e.g., swimming pools). Pinworm remains common in many areas, but it appears to be decreasing in prevalence. A survey of positive cellophane tape tests (see later) in New York City documented a sharp decline in positivity from 57 of 248 tests in 1971 to 17 of 165 in 1978 to 0 of 38 in 1986.[83] Similar trends are reported from California. Life Cycle E. vermicularis has a simple life cycle with a “hand to mouth” existence. The worm is acquired by ingesting parasite eggs. Most often these eggs are on the hands of the host; however, the small eggs also may become airborne, inhaled, and then swallowed. Eggs hatch in the duodenum, releasing larvae that molt twice as they mature and migrate to the cecum and ascending colon (Fig. 110-10, Video 110-3).[84] The parasites are small: adult males measure 0.2 mm by 2 to 5 mm, and adult females measure 0.5 mm by 8 to 13 mm. After mating, gravid females migrate to the rectum. During the night, egg-laden females migrate out of the anal canal and onto the perianal skin. Each female deposits up to 17,000 eggs, which mature rapidly, becoming infective within six hours. Pinworm infestation typically causes perianal itching, and scratching gathers eggs onto the hands, promoting reinfection and transmission to others.
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| Figure 110-10. Pinworm (Enterobius vermicularis, arrows) found on screening colonoscopy of an institutionalized man. | |
Clinical Features and Pathophysiology E. vermicularis is an extremely well adapted parasite that produces no specific symptoms in the vast majority of colonized persons. Most symptoms are minor, such as pruritus ani and restless sleeping. Rarely, pinworm causes eosinophilia or eosinophilic enteritis.[85] Vulvovaginitis is more common in girls with pinworm than in girls without this infection. Vulvovaginitis may be caused by migration of the worms into the introitus and genital tract. Dead worms and eggs encased in granulomas have been found in the cervix, endometrium, fallopian tubes, and peritoneum, attesting to the migratory effort of female worms.[86] Ectopic enterobiasis is rare and causes no or very little overt pathology. Infestation with E. vermicularis can influence mucosal immune responses. One case report described a 12-year-old girl with pinworm and apparently latent ulcerative colitis, who developed severe ulcerative colitis after treatment with pyrantel to remove the worms.[87] While she was colonized with E. vermicularis, intestinal biopsies showed increased expression of mRNA for IL-4, transforming growth factor (TGF)-β, IL-10, and FOXP3 compared with biopsy specimens taken after anthelminthic treatment; these transcripts are associated with immune regulatory pathways that suppress inflammation. Diagnosis E. vermicularis eggs are not plentiful in stool, an observation that might explain the low prevalence rates found in studies that only use stool specimens for diagnosis. The NIH cellophane tape test is the classic diagnostic test for pinworm. A two- to three-inch piece of clear tape is applied serially to several perianal areas in the morning before washing. The tape is then applied to a glass slide. Microscopic evaluation demonstrates parasite eggs that measure 30 by 60 ?m, have a thin shell, and appear flattened on one side. Three to seven daily samples are needed to exclude pinworm infestation. Treatment Pinworm actually requires no treatment unless the patient is symptomatic. It is highly transmittable, however, and for that reason should be expunged. E. vermicularis is readily treated with a single 100-mg dose of mebendazole or a 400-mg dose of albendazole. Reinfestation is common, and patients should receive a second treatment after 15 days. All members of the family should be treated and clothes and bed linens should be washed. Albendazole and mebendazole are potentially teratogenic. Because E. vermicularis has very low pathogenicity, treatment of pregnant women should be postponed until after delivery. TRICHINELLA SPECIES Trichinosis is a systemic illness caused by any of the eight closely related Trichinella species. People acquire the parasite by ingesting larvae present in raw or undercooked meat such as pork. Trichinosis has both intestinal and systemic phases characterized sequentially by nausea and diarrhea, fever, myalgia, and periorbital edema. Intense exposure can cause death due to severe myositis, neuritis, and thrombosis. Treatment is albendazole and glucocorticoids. Epidemiology Trichinosis is acquired by eating raw or undercooked meat that contains parasite larvae of Trichinella species. Worldwide, domestic pigs are the most common carriers. Trichinella species are divided into two groups,[88] one that forms encapsulated muscle cysts and only infests mammals (Trichinella spiralis, Trichinella britovi, Trichinella nelsoni, Trichinella native, Trichinella murrelli), and one that does not form encapsulated cysts and infests mammals and birds (Trichinella pseudospiralis) or mammals and reptiles (Trichinella papuae, Trichinella zimbabwensis). To date only T. zimbabwensis has not been implicated in human disease. These species are closely related, morphologically nearly identical, and distinguished using molecular approaches. Trichinella has worldwide distribution, with T. nativa and T. murrelli in the Arctic and subarctic regions; T. spiralis and T. pseudospiralis in the Americas, Europe, and Russia; T. britovi in Europe, north Africa, the Middle East, and Asia; T. nelsoni in equatorial Africa; T. zimbabwensis in Zimbabwe, Ethiopia, and Mozambique; and T. papuae only in Papua New Guinea. Each of the Trichinella species can infest any mammal. T. nativa is resistant to freezing for up to five years. Trichinosis was much more common in the United States than it is now. In the late 1940s, about 400 cases per year of symptomatic trichinosis were reported to various health agencies, and this number dropped to an average of 14.4 cases per year in the time period 1997 to 2001[89]; reports from Germany show a similar pattern.[90] This decrease is explained by two major factors: First is the strong admonition to thoroughly cook all pork products; second is a change in farming practice to now feed pigs only grain. Industrialized pig farms in North America have been free of trichinosis for more than 50 years, but trichinosis is a reemerging illness in eastern Europe, related to relaxed enforcement of regulations.[91] Currently, most reported cases involve a discrete exposure. For example, a 1991 outbreak in Wisconsin involved 40 people who ate pork sausage from one shop. A 1995 outbreak in Idaho involved 10 people who ate cougar jerky.[92] A 2005 outbreak in Canada involved at least 14 people who ate frozen then stewed black bear meat.[93] In France, several outbreaks have resulted from eating raw horse meat.[94] This emphasizes that all mammals including herbivores can transmit Trichinella.Life Cycle The same host harbors both the adult and larval form of Trichinella.[95] People acquire the parasite by eating raw or undercooked meat that contains encapsulated parasite larvae. Each cyst dissolves in the digestive tract, releasing one larva that invades the small intestinal mucosa and lives within the cytoplasm of about 45 villus cells (Fig. 110-11). Larvae mature rapidly and mate within 30 hours. Adults are minute: Male worms measure 60 ?m by 1.2 mm and female worms measure 90 ?m by 2.2 mm. Females are viviparous and begin releasing larvae about one week after their initial ingestion. Adults are short-lived, producing larvae for only four weeks, by which time they are expelled by the host.
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| Figure 110-11. Illustration of Trichinella spiralis coiled through enterocytes in the small intestine. Each Trichinella larva lives within the cytoplasm of approximately 45 villus cells. | |
The larvae live much longer than the adult worms. Larvae measure six by 100 ?m and enter the intestinal blood and lymphatic vessels. They are distributed by the circulatory system through the body but develop only within striated muscle. The larva enters a striated muscle fiber but does not kill the myocyte. Instead, it induces the cell to transform into a novel nurse cell that houses and feeds the parasite. The larva grows and develops into the infective stage in about five weeks. The coiled larvae remain viable for many years awaiting ingestion by another animal. Clinical Features and Pathophysiology Although most infestations with Trichinella are asymptomatic, significant exposure produces illness and even death.[96] Clinical trichinosis has two phases caused by the enteral (adult) and parenteral (larval) stages of the parasite. Intestinal symptoms result from enteritis due to adult worms that have embedded themselves in the intestinal epithelium. Enteritis produces abdominal pain, nausea, vomiting, diarrhea, and low-grade fever. Intestinal symptoms begin about two days to one week and peak at two weeks after ingestion of contaminated meat. The timing and severity of symptoms vary with intensity of exposure. The intestinal phase of trichinosis often is misdiagnosed as viral gastroenteritis or food poisoning. T. spiralis also infests mice and rats, permitting detailed study of the intestinal phase of infection.[97] Mice begin to expel adult worms about two weeks after initial infestation. Type 2 (Th2) cytokines (IL-4 and IL-5) promote worm expulsion. Expulsion of adult worms results from focal immune attack, increased secretions, and enhanced intestinal motility; T lymphocytes, eosinophils, and mast cells assist this primary response. Rats previously exposed to T. spiralis rapidly expel the parasite upon rechallenge, a protection likely resulting from an immediate-type hypersensitivity response to the parasite triggered by IgE-armed mast cells. The parenteral phase of trichinosis begins with the birth of migratory larvae about one week after ingestion of the contaminated meat. Larvae migrate into muscle and other organs such as the brain, spinal cord, and heart, evoking inflammatory responses; high fever, myalgia, periorbital edema, dysphagia, headache, and paresthesia result. Symptoms peak about four to five weeks after initial exposure and can take months to resolve. The severity and timing of symptoms vary with the intensity of exposure. Many patients develop systemic complaints without prior intestinal symptoms. The inflammatory response to migrating larvae produces myositis. Patients have eosinophilia and an elevated serum level of creatine phosphokinase (CPK). An intense exposure can cause fatal myocarditis, neuritis, and vasculitis or thrombosis. Patients are at highest risk of death between the third and sixth week after exposure. Because trichinosis is rare, index cases often are misdiagnosed initially. Numerous persons presenting in a narrow time frame and with similar and compatible symptoms should prompt consideration of trichinosis as the diagnosis. Diagnosis Trichinella cannot by diagnosed by stool examination or intestinal biopsy. Trichinella species do not lay eggs, and no larvae are present in stool specimens. Even with heavy infestations, adult worms are too uncommon to be found by random biopsy. Diagnosis is made by muscle biopsy demonstrating larvae within nurse cells. Diagnosis also can be made by serology. Acute and convalescent serum samples confirm a rise in anti-Trichinella antibody. Treatment Although adults are short-lived, treatment with albendazole 400 mg twice a day or mebendazole 5 mg/kg/day for 10 to 15 days[98] is warranted and abbreviates the production of larvae by adult worms. Addition of glucocorticoids reduces inflammation and systemic symptoms; however, glucocorticoids given in the absence of a benzimidazole can prolong the intestinal phase, increasing the number of larvae released. ANISAKIS SIMPLEX A. simplex and another anisakid, Pseudoterranova decipiens, can infect people transiently, causing abdominal pain, hematemesis, or intestinal inflammation. A. simplex is also a potent allergen that might explain some cases of fish allergy. Anisakidosis is acquired by eating raw or undercooked fish. No treatment is usually required. Epidemiology and Life Cycle A. simplex and P. decipiens infest fish and marine mammals.[99] People become accidental hosts by eating raw or pickled fish. Anisakidosis has become more common with the increased popularity of eating raw fish (e.g., sushi). Many species of saltwater fish harbor A. simplex larvae including herring, mackerel, salmon, plaice, and squid. The parasite larvae initially infest crustaceans that are consumed by fish. The larvae migrate to the fish musculature and, if a parasitized fish is eaten by another fish, the larvae again migrate to the musculature of their new host. Eventually, a parasitized fish is eaten by a marine mammal that serves as the definitive host. In the marine mammal, the parasite larvae mature into adult intestinal worms and lay eggs that are passed with feces, the eggs hatch to release larvae that infest crustaceans, and the life cycle is thus renewed. Clinical Features and Pathophysiology A. simplex and P. decipiens cause transient infestations in humans. They do not reach full maturity in humans and therefore produce no eggs. The most common gastrointestinal symptom is acute severe stomach pain with nausea and hematemesis shortly after eating larva-infested raw fish. Endoscopy may demonstrate a small larva partially penetrating the gastric or intestinal wall.[100,101] Rarely, A. simplex can enter the intestinal wall and cause a strong inflammatory reaction that can mimic acute appendicitis[102] or Crohn's disease. Human infestations with either A. simplex or P. decipiens is termed anisakidosis after the family name (Anisakidae) for these parasites. A. simplex is a potent allergen, and many cases of seafood (fish) allergy actually may be reactions to A. simplex,[103] including anaphylaxis from well-cooked marine fish.[99,104] In Spain, 12% to 22% of persons are seropositive for IgE against A. simplex.[105,106]Diagnosis and Treatment A history of recent (within three days) ingestion of raw fish suggests anisakidosis in the appropriately symptomatic patient. Diagnosis is made by finding the larvae on endoscopy or in surgically excised specimens. Gastric anisakidosis is diagnosed by endoscopy, and endoscopic removal of the anisakid alleviates symptoms. Intestinal anisakidosis can prompt surgery for patients presenting with symptoms of acute small bowel obstruction or peritonitis,[107] but surgery may be avoidable if a recent history of eating raw fish is elicited and conservative treatment is tolerated.[108] A. simplex and P. decipiens infestations are transient because the parasites do not survive in humans. Therefore, treatment with an anthelminthic is not needed.
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