111 HELMINTHIC INFECTIONS AND ECTOPARASITE INFESTATIONS
Harrison’s Manual of Medicine
HELMINTHIC INFECTIONS AND ECTOPARASITE INFESTATIONS
Visceral and Ocular Larva Migrans
Cutaneous Larva Migrans
Taeniasis and Diphyllobothriasis
EPIDEMIOLOGY Trichinella spp. infect carnivorous and omnivorous animals worldwide. Both humans and animals acquire the infection by ingesting meat containing encysted Trichinella larvae. Swine are the most common human vector. Around 40 human cases are reported in the U.S. each year; however, most mild cases probably remain undiagnosed. Recent U.S. outbreaks have been attributed to undercooked pork, homemade and commercial sausage, wild boar, and walrus meat.
PATHOGENESIS AND CLINICAL MANIFESTATIONS Light infections (<10 larvae per gram of muscle) are usually asymptomatic. With heavy infection (>50 larvae per gram of muscle), clinical symptoms parallel the stages of the parasite’s life cycle: Enteric invasion during the first week may cause diarrhea or constipation, abdominal pain, nausea, and vomiting. Larval migration during the second week is associated with fever, hypereosinophilia, periorbital and facial edema, and splinter hemorrhages. Maculopapular rash, myocarditis, pneumonitis, or encephalitis may develop. Encystment of larvae in muscle beginning in the second to third week is associated with myalgia, muscle edema, and weakness. The most commonly involved muscle groups are the extraocular muscles, the biceps, and the muscles of the jaw, neck, lower back, and diaphragm.
DIAGNOSIS The diagnosis is made histologically by the finding of larvae in a fresh specimen of muscle, which should be compressed between glass slides and examined microscopically. At least 1 g of involved muscle should be biopsied. The yield is highest near tendinous insertions. A rise in the titer of parasite- specific antibody may also be diagnostic but usually does not occur until after the third week of infection. Eosinophilia may peak at >50% between 2 and 4 weeks after infection. Serum levels of IgE, creatine phosphokinase, lactate dehydrogenase, and aspartate aminotransferase are elevated in most symptomatic pts.
No agents are currently available for the treatment of Trichinella larvae in muscle. Thiabendazole (25 mg/kg PO bid for 5–7 d) and mebendazole (400 mg PO tid) are active against the early, enteric stage of the infection. For cases with severe myositis or myocarditis, prednisone (1 mg/kg PO qd for 5 d) is beneficial. Most lightly infected pts recover uneventfully.
PREVENTION Larvae encysted in pork may be killed by cooking the meat until it is no longer pink or by freezing it at –15°C for 3 weeks. T. nativa, the species prevalent among arctic carnivores, is relatively tolerant of freezing.
VISCERAL AND OCULAR LARVA MIGRANS
PATHOGENESIS AND EPIDEMIOLOGY Visceral larva migrans (toxocariasis) is a syndrome caused by nematodes parasitic for nonhuman species. Human infection is a dead end for the parasite. The nematode larvae do not develop into adult worms. Instead, their migration through host tissues elicits an eosinophilic inflammatory response. Humans acquire toxocariasis mainly by eating soil contaminated with puppy feces containing infective Toxocara canis eggs. Seropositivity rates may exceed 20% among U.S. kindergarten children.
CLINICAL MANIFESTATIONS Most light infections are asymptomatic; eosinophilia may be the lone clue. Characteristic manifestations of heavier infection include fever, malaise, anorexia, weight loss, cough, wheezing, rash, and hepatosplenomegaly. Extraordinary eosinophilia is often present; eosinophils may constitute 90% of the WBCs. Half of pts with symptomatic pneumonitis have transient pulmonary infiltrates. Ocular disease occurs when larvae invade the eye. A granulomatous mass develops around the larvae and may be mistaken for retinoblastoma. The spectrum of ocular involvement also includes endophthalmitis, uveitis, and chorioretinitis.
DIAGNOSIS The clinical diagnosis of toxocariasis is confirmed by an ELISA positive for toxocaral antibodies. Since Toxocara larvae do not develop into adult worms in humans, eggs are not found in the stool.
Available anthelmintic drugs have not been shown conclusively to alter the course of larva migrans. In pts with severe disease, glucocorticoids may be used to reduce inflammatory complications. For ocular disease, treatment is unsatisfactory; the roles of glucocorticoids and anthelmintics are controversial.
CUTANEOUS LARVA MIGRANS
Cutaneous larva migrans (“creeping eruption”) is a serpiginous skin eruption caused by burrowing larvae of animal hookworms, most commonly Ancylostoma braziliense.
PATHOGENESIS AND CLINICAL MANIFESTATIONS Larvae hatch from eggs passed in canine or feline feces and mature in the soil, after which they can penetrate human skin to initiate infection. Erythematous, pruritic lesions form along the tortuous tracks of their migration; the larvae may advance several centimeters per day.
DIAGNOSIS The diagnosis is readily made on clinical grounds. A skin biopsy rarely yields diagnostic material.
Without treatment, larvae die out after several weeks. Symptoms are alleviated by treatment with thiabendazole (25 mg/kg PO bid or a 10% suspension applied topically for 2–5 d), ivermectin (a single dose of 150–200 µg/kg), or albendazole (200 mg bid for 2 d).
Ascaris lumbricoides (roundworm) is the largest intestinal nematode parasite of humans, reaching up to 40 cm in length.
EPIDEMIOLOGY Ascaris is widely distributed in tropical and subtropical regions and in other humid areas, such as the rural southeastern U.S. Younger children in impoverished rural areas are most affected.
PATHOGENESIS Infective eggs present in soil are ingested. Larvae hatch in the intestine, traverse the mucosa to gain access to the bloodstream, and are transported to the lung, where they break into the alveoli, ascend the bronchial tree, are swallowed, and return to the small intestine. There they become adult worms. Mature females produce many thousands of eggs each day.
CLINICAL MANIFESTATIONS Clinical disease arises from pulmonary hypersensitivity or from intestinal events. Fever, cough, and eosinophilia may develop during the stage of pulmonary migration. Eosinophilic pneumonitis (Loeffler’s syndrome) may be evident on CXR. Light intestinal infection is usually asymptomatic. A heavy intestinal burden of adult worms may cause obstruction and malabsorption. A lone worm migrating to aberrant sites (e.g., the biliary tree) may also cause disease. Migration of a worm up the esophagus can cause coughing and oral expulsion.
DIAGNOSIS The characteristic eggs may be seen on microscopic examination of stool. Adult worms may be passed in the stool or through the mouth or nose. Larvae can be found in the sputum during the transpulmonary migratory phase. Large adult worms may be serendipitously visualized on contrast studies of the GI tract.
Mebendazole and albendazole are effective, but their use is contraindicated in pregnancy or for heavy infection. Pyrantel pamoate and piperazine citrate are safe in pregnancy. Intestinal obstruction should be managed by nasogastric suction, IV fluid administration, and instillation of piperazine through the nasogastric tube. Worms in the biliary tract may require extraction via endoscopy.
Strongyloides stercoralis is distinguished by a capacity, unusual among helminths, to replicate in humans. This capacity permits ongoing cycles of autoinfection from endogenously produced larvae. Strongyloidiasis can thus persist for decades; at times of host immunocompromise, the larvae may disseminate widely, with catastrophic results (autoinfection syndrome).
EPIDEMIOLOGY S. stercoralis is spottily distributed in tropical areas and other hot, humid regions. It is endemic in parts of the southern U.S. This nematode is also found among residents of mental institutions, where hygiene may be poor, and among persons who have lived in endemic areas abroad.
PATHOGENESIS Filariform larvae in fecally contaminated soil penetrate human skin, travel via the bloodstream to the lung, penetrate into the alveoli, ascend the airway, are swallowed, reach the small bowel, and there mature into adult worms. In autoinfection, larvae invade through the colonic wall or perianal skin.
CLINICAL MANIFESTATIONS In uncomplicated strongyloidiasis, pts may be asymptomatic or have mild cutaneous and/or abdominal symptoms, including recurrent urticaria (especially involving the wrists and/or buttocks), “larva currens” (a pathognomonic response to subcutaneous migrating larvae, which may advance up to 10 cm/h), nausea, diarrhea, GI bleeding, and epigastric pain aggravated by eating. Eosinophilia is common and may fluctuate with time. Pulmonary symptoms are rare. In autoinfection syndrome, larvae may invade the GI tract, lungs, CNS, liver, kidneys, and peritoneum and may facilitate the development of gram-negative sepsis, pneumonia, or meningitis. Disseminated strongyloidiasis, especially in pts who are given steroids, can be fatal.
DIAGNOSIS In uncomplicated strongyloidiasis, the finding of rhabditiform larvae in stool or intestinal aspirates is diagnostic. Eggs are almost never detectable in the stool. A sensitive ELISA for Strongyloides antigens is available. For suspected disseminated strongyloidiasis, filariform larvae should be sought in stool, sputum, and other sites of potential dissemination.
Even in the asymptomatic state, strongyloidiasis should be treated. Ivermectin (200 µg/kg qd for 1–2 d) is more effective and better tolerated than thiabendazole (25 mg/kg PO bid for 2 d). For disseminated infection, treatment should be extended for at least 5–7 d.
PATHOGENESIS AND EPIDEMIOLOGY The agents of lymphatic filariasis (Wuchereria bancrofti throughout the tropics and subtropics, Brugia malayi in India and the Far East, and Brugia timori in Indonesia) are transmitted by mosquitoes. An estimated 115 million people are affected. The adult filariae reside in lymphatics and lymph node sinuses. The presence of the worms and the host’s inflammatory response to them lead to lymphatic compromise. Death of the worms enhances inflammation and fibrosis, ultimately causing lymphatic obstruction and lymphedema.
CLINICAL MANIFESTATIONS Common manifestations include asymptomatic microfilaremia, hydrocele, acute adenolymphangitis, chronic lymphatic disease, and lymphatic obstruction and the permanent changes associated with elephantiasis.
DIAGNOSIS A definitive diagnosis is made only by detection of the parasite, which can be difficult. By virtue of their location in lymphatics, the adults are inaccessible. Microfilariae should be sought in blood and hydrocele fluid. The timing of blood sampling is critical and should be based on the periodicity of the microfilariae suspected to be involved. Assays for circulating antigens of W. bancrofti are highly sensitive and specific. Antibody assays are complicated by cross-reactivity with other helminths. PCR-based assays have been developed for W. bancrofti and B. malayi.
Therapy with diethylcarbamazine (DEC, 6 mg/kg daily in either single or divided doses for 12 d) clears microfilariae. To minimize acute reactions to antigens released by dying filariae, gradual upward titration of the DEC dose or premedication with glucocorticoids may be useful.
EPIDEMIOLOGY Onchocerciasis (“river blindness”) is caused by the filarial nematode Onchocerca volvulus. Some 13 million people are infected in equatorial Africa and Latin America. Onchocerciasis is the second leading infectious cause of blindness worldwide.
PATHOGENESIS Infective larvae are deposited on human skin by the bites of infected blackflies. The larvae develop into adults, which reside in subcutaneous nodules. After an interval ranging from months to ~3 years, microfilariae begin to be released, migrate out of the nodule and throughout the tissues, and concentrate in the dermis. Onchocerciasis affects primarily the skin, eyes, and lymph nodes. The damage is elicited by the microfilariae, not by the adult worms.
CLINICAL MANIFESTATIONS Pruritus and generalized papular rash are common; the pruritus can be incapacitating. Subcutaneous onchocercomata contain adult worms. Lesions may develop in any part of the eye. Ocular lesions include sclerosing keratitis (the leading cause of onchocercal blindness in Africa), anterior uveitis, iridocyclitis, and chorioretinal atrophy. Secondary glaucoma or optic atrophy may occur.
DIAGNOSIS Definitive diagnosis depends on detection of an adult worm in an excised nodule or of microfilariae in a skin snip. For identification of the latter form, snips should be incubated for 2–4 h in tissue culture medium or in saline on a glass slide or a flat-bottomed microtiter plate and examined by low- power microscopy. Antibody detection as well as PCR are highly sensitive and specific and are used in specialized laboratories.
The main goals of therapy are to prevent the development of irreversible lesions and to ease symptoms. Nodules on the head must be excised to avoid ocular infection. Ivermectin is administered orally in a single dose of 150 µg/ kg, either annually or semiannually. Contraindications to treatment include pregnancy, breast-feeding, CNS disorders that compromise the blood-brain barrier, and an age of <5 years. Ivermectin does not kill adult worms.
EPIDEMIOLOGY Schistosoma mansoni is found in parts of South America, Africa, and the Middle East; S. japonicum, in China, the Philippines, and Indonesia; S. haematobium, in Africa and the Middle East; and S. mekongi, along the Mekong River in Southeast Asia. Worldwide, some 200–300 million people may be infected with schistosomes. Only a small minority of them develop significant disease.
PATHOGENESIS Cercariae, released from freshwater snails, penetrate unbroken human skin. As they mature into schistosomes, they reach the portal vein, where males and females pair. They then migrate to the venules of the bladder and ureters (S. haematobium) or mesentery (S. mansoni, S. japonicum, S. mekongi) and begin to deposit eggs. Some mature ova are extruded into the intestinal or urinary lumina, from which they may reach water and perpetuate the life cycle. The persistence of other ova in tissues leads to a granulomatous host response and fibrosis. Factors governing disease manifestations include the intensity and duration of infection, the location of egg deposition, and the genetic characteristics of the host.
CLINICAL MANIFESTATIONS Dermatitis (“swimmer’s itch”) may result from cercarial invasion by S. mansoni and S. japonicum. Acute schistosomiasis, or Katayama fever, is a serum sickness–like syndrome associated with fever, lymphadenopathy, and hepatosplenomegaly; it occurs in visitors to endemic areas and lasts up to 3 months. Chronic infection with S. mansoni, S. japonicum, or S. mekongi manifests as an initial intestinal phase of colicky abdominal pain and bloody diarrhea followed by hepatomegaly from granulomatous liver lesions and eventually peripheral fibrosis with portal hypertension, splenomegaly, and esophageal varices. S. haematobium prefers the veins of the urinary tract. It may cause hematuria and dysuria at all stages of infection and may produce ureteral and vesicular fibrosis and calcification in the chronic stage. Squamous cell carcinoma of the bladder has been associated with S. haematobium infection.
DIAGNOSIS Two serologic tests available through the CDC are highly sensitive and specific. In some instances, examination of the stool or urine for ova may yield positive results.
Praziquantel results in parasitologic cure in ~85% of cases. Recommended doses are 20 mg/kg bid for S. mansoni and S. haematobium infections and 20 mg/kg tid for S. japonicum and S. mekongi infections.
TAENIASIS AND DIPHYLLOBOTHRIASIS
PATHOGENESIS Cysticercal larvae are ingested in undercooked beef (Taenia saginata), pork (Taenia solium), or fish (Diphyllobothrium latum) and develop into mature tapeworms within the definitive human host. For T. solium, humans can also be the intermediate host: ingestion of T. solium eggs, their embryonation, and dissemination of the larvae lead to cysticercosis.
CLINICAL MANIFESTATIONS T. saginata and T. solium infections may be asymptomatic or may cause mild abdominal discomfort, nausea, change in appetite, and/or weight loss. Proglottids may be visible in stool. D. latum infections are associated with vitamin B12 deficiency. Cysticerci of T. solium can be found anywhere in the body, most commonly in the brain and skeletal muscle. CNS cysticercosis can result in seizures, hydrocephalus, and signs of elevated intracranial pressure.
DIAGNOSIS Infections with T. saginata and T. solium are diagnosed by detecting eggs or proglottids in the stool; distinguishing between the two species requires examination of mature proglottids or the scolex. The diagnostic criteria for cysticercosis are listed in Table 111-1.
Table 111-1 Proposed Diagnostic Criteria for Human Cysticercosis, 1996
For infection with adult worms, a single dose of praziquantel (5–10 mg/kg) is highly effective. Vitamin B12 should be given parenterally if the pt is B12 deficient. Four placebo-controlled trials failed to identify any clinical advantage of antiparasitic drugs for parenchymal neurocysticercosis. However, some authorities favor treatment of these cases in light of trends toward faster resolution of neuroradiologic abnormalities. Treatment of the symptoms of neurocysticercosis consists of praziquantel (50–60 mg/kg qd in 3 doses for 15 d or 100 mg/kg given in three doses over a single day) or albendazole (15 mg/kg qd in 3 doses for 8–28 d); hospitalization and concomitant glucocorticoid therapy are advisable if symptoms worsen during treatment. Ocular, spinal, or cerebral ventricular lesions may require excision.
PATHOGENESIS AND EPIDEMIOLOGY Infection occurs through human ingestion of eggs of the dog tapeworms. Embryos penetrate the intestinal mucosa, enter the portal circulation, and disseminate to various organs, especially the liver and lungs. Brood capsules and daughter cysts develop within hydatid cysts. New larvae, called scolices, develop within the brood capsules. Echinococcus granulosus occurs in livestock-raising regions outside North America. E. multilocularis predominates in arctic and subarctic zones. E. vogeli is found only in Central and South America. E. multilocularis vesicles are locally invasive.
CLINICAL MANIFESTATIONS Enlargement of cysts may progress for 5–20 years before the development of symptoms, which are typically related to compressive or mass effects. Hepatic echinococcosis may present as abdominal pain, a palpable RUQ mass, or biliary obstruction. Cyst rupture may produce fever, pruritus, urticaria, or anaphylaxis and leads to multifocal dissemination. E. multilocularis infection mimics hepatic malignancy, with liver destruction, extension into vital structures, and (in occasional cases) metastasis.
DIAGNOSIS The CT finding of daughter cysts within the larger cyst is pathognomonic for E. granulosus infection. MRI, ultrasound, and—for pulmonary disease—plain films may be diagnostically helpful. Calcification may be evident in liver cyst walls. Serology is negative in up to 50% of pts with pulmonary echinococcosis but is positive in ~90% of cases with liver involvement. Aspiration poses a risk of rupture and dissemination and is not usually recommended; however, if aspiration is performed, demonstration of scoliceal hooklets solidifies the diagnosis.
Both surgical excision and repeated aspiration and instillation of scolicidal agents have been advocated to remove the cyst. Albendazole (15 mg/kg qd in two divided doses) should be administered before the procedure and continued thereafter for several weeks in E. granulosus infection and for up to 2 years in E. multilocularis infection. Albendazole therapy results in cure in ~30% of cases. Multiple courses of treatment may be necessary.
Ectoparasites are arthropods or helminths that infest the skin of other animals from which they derive sustenance. They damage their hosts by inflicting direct injury, eliciting hypersensitivity, or inoculating toxins or pathogens.
The human itch mite, Sarcoptes scabiei, infests 300 million persons per year. Itching and rash are the results of a sensitization reaction to the excreta of female mites that burrow beneath the stratum corneum to deposit eggs. Intimate contact is generally required for person-to-person transmission; sharing of contaminated garments is an infrequent mode of transmission. Burrows appear as dark wavy lines in the epidermis, at one end of which is a small bleb containing the female mite. Excoriated papules and vesicles are symmetrically distributed over the volar wrists, between the fingers, on the penis, and in skin folds. Hyperinfestation may occur in immunodeficient pts and results in thick keratotic crusts with fissuring, a condition known as Norwegian scabies or crusted scabies. Bacteremia may result from secondary infection of the lesions. Diagnosis is made by microscopic demonstration of the mite, its eggs, and its feces in scrapings of lesions. For treatment, 5% permethrin cream is less toxic than 1% lindane and is effective against lindane-tolerant infestations. Both agents are applied behind the ears and from the neck down, left on for 8 h, and washed off. Lindane should not be used in childhood or pregnancy. Alternatives are crotamiton cream, benzyl benzoate, and sulfur ointments. A single oral dose of ivermectin (200 µg/kg) is effective for treatment of scabies in healthy persons but has not yet been approved by the FDA. Treated pts become noninfectious within a day, although itching may persist for weeks or months and should be treated with antipruritics. Bedding and clothing should be washed, and all close contacts should be treated regardless of symptoms.
All three species of human louse—Pediculus humanus var. capitis (the head louse), P. humanus var. corporis (the body louse, which infests clothing), and Phthirus pubis (the pubic louse)—feed at least once a day on human blood. Itching results from sensitization to the saliva of the lice. Head lice are transmitted between schoolchildren, body lice are transmitted between persons who do not change their clothes often, and pubic lice are usually sexually transmitted. Body lice can transmit typhus, relapsing fever, or trench fever. Diagnosis is made by observation of the 2- to 4-mm-long lice or their nits, which are white or cream colored (head and body lice) or dark brown (pubic lice). The preferred treatment is a single application of 1% permethrin cream rinse, which kills both lice and eggs; 0.5% malathion is an alternative but must be left on for 8–12 h. Lindane (1%) and pyrethrins are not ovicidal and require a second application 1 week after the first. The hair should be combed with a fine-toothed comb to remove nits. Pediculicides must be applied from head to foot to remove body lice. Clothes and bedding should be deloused by placement in a hot dryer for 30 min or by fumigation.
Tunga penetrans is also known as the jigger, sand flea, or chigoe flea. Adults live in sandy soil and burrow under the skin between toes, under nails, or on the soles of the feet. Lesions resemble a white pustule with a central black depression and may be pruritic or painful. Treatment entails removal of the intact flea with a needle or scalpel, tetanus prophylaxis, and topical antibiotic application.
For a more detailed discussion, see Weller PF, Liu LX: Trichinella and Other Tissue Nematodes, Chap. 219, p. 1231; Weller PF, Nutman TB: Intestinal Nematodes, Chap. 220, p. 1233; Nutman TB, Weller PF: Filariasis and Related Infections (Loiasis, Onchocerciasis, and Dracunculiasis), Chap. 221, p. 1237; Mahmoud AAF: Schistosomiasis and Other Trematode Infections, Chap. 222, p. 1242; White AC Jr, Weller PF: Cestodes, Chap. 223, p. 1248; and Maguire JH, Spielman A: Ectoparasite Infestations, Arthropod Bites and Stings, Chap. 398, p. 2622, in HPIM-15.