1766 PART 5 Infectious Diseases

in turn enter and infect intestinal epithelial cells. The parasite’s further

development involves both asexual and sexual cycles, which produce

forms capable of infecting other epithelial cells and of generating

oocysts that are passed in the feces. Cryptosporidium species infect a

number of animals, and C. parvum can spread from infected animals

to humans. Since oocysts are immediately infectious when passed in

feces, person-to-person transmission takes place in day-care centers

and among household contacts and medical providers. Waterborne

transmission (especially that of C. hominis) accounts for infections in

travelers and for common-source epidemics. Oocysts are quite hardy

and resist killing by routine chlorination. Both drinking water and

recreational water (e.g., pools, waterslides) have been increasingly recognized as sources of infection.

Pathophysiology Although intestinal epithelial cells harbor cryptosporidia in an intracellular vacuole, the means by which secretory

diarrhea is elicited remain uncertain. No characteristic pathologic

changes are found by biopsy. The distribution of infection can be spotty

within the principal site of infection, the small bowel. Cryptosporidia

are found in the pharynx, stomach, and large bowel of some patients

and at times in the respiratory tract. Especially in patients with AIDS,

involvement of the biliary tract can cause papillary stenosis, sclerosing

cholangitis, or cholecystitis.

Clinical Manifestations Asymptomatic infections can occur in

both immunocompetent and immunocompromised hosts. In immunocompetent persons, symptoms develop after an incubation period of

~1 week and consist principally of watery nonbloody diarrhea, sometimes in conjunction with abdominal pain, nausea, anorexia, fever, and/

or weight loss. In these hosts, the illness usually subsides after 1–2 weeks.

In contrast, in immunocompromised hosts (especially those with AIDS

and CD4+ T-cell counts <100/μL), diarrhea can be chronic, persistent,

and remarkably profuse, causing clinically significant fluid and electrolyte depletion. Stool volumes may range from 1 to 25 L/d. Weight loss,

wasting, and abdominal pain may be severe. Biliary tract involvement

can manifest as mid-epigastric or right-upper-quadrant pain.

Diagnosis (Table 229-1) Evaluation starts with fecal examination

for small oocysts, which are smaller (4–5 μm in diameter) than the

fecal stages of most other parasites. Because conventional stool examination for ova and parasites (O+P) does not detect Cryptosporidium,

specific testing must be requested. Detection is enhanced by evaluation

of stools (obtained on multiple days) by several techniques, including

modified acid-fast and direct immunofluorescent stains and enzyme

immunoassays. NAATs are also useful. Cryptosporidia can also be

identified by light and electron microscopy at the apical surfaces of

intestinal epithelium from biopsy specimens of the small bowel and,

less frequently, the large bowel.

TREATMENT

Cryptosporidiosis

Nitazoxanide, approved by the U.S. Food and Drug Administration

(FDA) for the treatment of cryptosporidiosis, is available in tablet

form for adults (500 mg twice daily for 3 days) and as an elixir for

children. This agent has not been effective for the treatment of

immunosuppressed patients or HIV-infected patients, in whom

improved immune status due to antiretroviral therapy can lead to

amelioration of cryptosporidiosis. Otherwise, treatment includes

supportive care with replacement of fluids and electrolytes and

administration of antidiarrheal agents. Biliary tract obstruction

may require papillotomy or T-tube placement. Prevention requires

minimizing exposure to infectious oocysts in human or animal

feces. Use of submicron water filters may minimize acquisition of

infection from drinking water.

■ CYSTOISOSPORIASIS

The coccidian parasite Cystoisospora belli causes human intestinal disease. Infection is acquired by the consumption of oocysts, after which

the parasite invades intestinal epithelial cells and undergoes both

sexual and asexual cycles of development. Oocysts excreted in stool

are not immediately infectious but must undergo further maturation.

Although C. belli infects many animals, little is known about the

epidemiology or prevalence of this parasite in humans. It is most

common in tropical and subtropical countries. Acute infections can

begin abruptly with fever, abdominal pain, and watery nonbloody

diarrhea and can last for weeks or months. In patients who have AIDS

or are immunocompromised for other reasons, infections often are not

self-limited but rather resemble cryptosporidiosis, with chronic, profuse watery diarrhea. Eosinophilia, which is not found in other enteric

protozoan infections, may be detectable. The diagnosis (Table 229-1)

is usually made by detection of the large (~25 μm) oocysts in stool by

modified acid-fast staining. Oocyst excretion may be low-level and

intermittent; if repeated stool examinations are unrevealing, sampling

of duodenal contents by aspiration or small-bowel biopsy (often with

electron microscopic examination) may be necessary. NAATs are effective newer diagnostic tools.

TREATMENT

Cystoisosporiasis

Trimethoprim-sulfamethoxazole (TMP-SMX, 160/800 mg two

times daily for 10 days; and, for HIV-infected patients, then continuing three times daily for 3 weeks) is effective. For patients intolerant of sulfonamides, pyrimethamine (50–75 mg/d) can be used.

Relapses can occur in persons with AIDS and necessitate maintenance therapy with TMP-SMX (160/800 mg three times per week).

■ CYCLOSPORIASIS

Cyclospora cayetanensis, a cause of diarrheal illness, is globally distributed: illness due to C. cayetanensis has been reported in the United

States, Asia, Africa, Latin America, and Europe. The epidemiology of this

parasite has not yet been fully defined, but waterborne transmission and

foodborne transmission (e.g., by basil, sweet peas, and imported raspberries) have been recognized. The full spectrum of illness attributable

to Cyclospora has not been delineated. Some infected patients may be

without symptoms, but many have diarrhea, flulike symptoms, and flatulence and belching. The illness can be self-limited, can wax and wane,

or, in many cases, can involve prolonged diarrhea, anorexia, and upper

gastrointestinal symptoms, with sustained fatigue and weight loss in

some instances. Diarrheal illness may persist for >1 month. Cyclospora

can cause enteric illness in patients infected with HIV.

The parasite is detectable in epithelial cells of small-bowel biopsy

samples and elicits secretory diarrhea by unknown means. The absence

of fecal blood and leukocytes indicates that disease due to Cyclospora

is not caused by destruction of the small-bowel mucosa. The diagnosis (Table 229-1) can be made by detection of spherical 8- to 10-μm

oocysts in the stool, although routine stool O+P examinations are not

sufficient. Specific fecal examinations must be requested to detect the

oocysts, which are variably acid-fast and are fluorescent when viewed

with ultraviolet light microscopy. NAATs are proving to be sensitive.

Cyclosporiasis should be considered in the differential diagnosis of

prolonged diarrhea, with or without a history of travel by the patient

to other countries.

TREATMENT

Cyclosporiasis

Cyclosporiasis is treated with TMP-SMX (160/800 mg twice daily

for 7–10 days). HIV-infected patients may experience relapses

after such treatment and thus may require longer-term suppressive

maintenance therapy.

■ MICROSPORIDIOSIS

Microsporidia are obligate intracellular spore-forming protozoa that

infect many animals and cause disease in humans, especially as

1767CHAPTER 229 Protozoal Intestinal Infections and Trichomoniasis

Intracellular

multiplication

via merogony and

sporogony

Microsporidia

Enterocytozoon bieneusi, Encephalitozoon spp., etc.

Encephalitozoon intestinalis

in epithelial cells, endothelial

cells, or macrophages

E. bieneusi

in epithelial cell

Polar tubule pierces

host epithelial cell,

injects sporoplasm

Presumed

ingestion or

respiratory

acquisition of

spores

Person-to-person,

zoonotic,

waterborne, or

food-borne

transmission?

Diagnostic spores present

in stool, urine, respiratory fluids,

cerebrospinal fluid, or

various tissue specimens

Sloughed cells

degenerate;

spores shed in

bodily fluids

Spore-laden

host epithelial

cells sloughed

into lumina of

gastrointestinal,

respiratory, or

genitourinary tract

While E. bieneusi is

primarily in the gastrointestinal tract,

other species may invade the lung

or eye or disseminate to cause:

Chronic diarrhea

Cholangitis

Sinusitis

Bronchitis

Nephritis

Cystitis/prostatitis

Keratoconjunctivitis

Encephalitis

FIGURE 229-3 Life cycle of microsporidia. (Reproduced with permission from RL Guerrant et al [eds]: Tropical

Infectious Diseases: Principles, Pathogens and Practice, 2nd ed, Elsevier 2006.)

opportunistic pathogens in AIDS. Microsporidia

are members of a distinct phylum, Microspora,

which contains dozens of genera and hundreds

of species. The various microsporidia are differentiated by their developmental life cycles,

ultrastructural features, and molecular taxonomy based on ribosomal RNA. The complex life

cycles of the organisms result in the production of

infectious spores (Fig. 229-3). Currently, at least

15 species of microsporidia, including the genera Encephalitozoon, Tubulinosema, Pleistophora,

Nosema, Vittaforma, Trachipleistophora, Anncaliia, Microsporidium, and Enterocytozoon, are

recognized as causes of human disease. Although

some microsporidia are probably prevalent

causes of self-limited or asymptomatic infections

in immunocompetent patients, little is known

about how microsporidiosis is acquired.

Microsporidiosis is most common among

patients with AIDS, less common among patients

with other types of immunocompromise, and

rare among immunocompetent hosts. In patients

with AIDS, intestinal infections with Enterocytozoon bieneusi and Encephalitozoon intestinalis

are recognized to contribute to chronic diarrhea

and wasting; these infections have been found

in 10–40% of patients with chronic diarrhea.

Both organisms have been found in the biliary

tracts of patients with cholecystitis. E. intestinalis may also disseminate to cause fever, diarrhea, sinusitis, cholangitis, and bronchiolitis. In

patients with AIDS, Encephalitozoon hellem has

caused superficial keratoconjunctivitis as well as

sinusitis, respiratory tract disease, and disseminated infection. Myositis due to Pleistophora

has been documented. Nosema, Vittaforma, and

Microsporidium have caused stromal keratitis

associated with trauma in immunocompetent

patients.

Microsporidia are small gram-positive organisms with mature spores measuring 0.5–2 μm ×

1–4 μm. Diagnosis of microsporidial infections

in tissue often requires electron microscopy,

although intracellular spores can be visualized by light microscopy with hematoxylin and

eosin, Giemsa, or tissue Gram’s stain. For the diagnosis of intestinal

microsporidiosis, modified trichrome or chromotrope 2R–based staining and Uvitex 2B or calcofluor fluorescent staining reveal spores in

smears of feces or duodenal aspirates. NAATs are useful for diagnosis

and speciation. Definitive therapies for microsporidial infections

remain to be established. For superficial keratoconjunctivitis due to

E. hellem, E. cuniculi, E. intestinalis, and E. bieneusi, topical therapy

with fumagillin suspension has shown promise (Chap. 222). For

enteric infections with E. intestinalis in HIV-infected patients, therapy

with albendazole may be efficacious (Chap. 222).

■ OTHER INTESTINAL PROTOZOA

Balantidiasis Balantidium coli is a large ciliated protozoal parasite

that can produce a spectrum of large-intestinal disease analogous to

amebiasis. The parasite is widely distributed in the world. Since it

infects pigs, cases in humans are more common where pigs are raised.

Infective cysts can be transmitted from person to person and through

water, but many cases are due to the ingestion of cysts derived from

porcine feces in association with slaughtering, with use of pig feces for

fertilizer, or with contamination of water supplies by pig feces.

Ingested cysts liberate trophozoites, which reside and replicate in

the large bowel. Many patients remain asymptomatic, but some have

persisting intermittent diarrhea, and a few develop more fulminant

dysentery. In symptomatic individuals, the pathology in the bowel—

both gross and microscopic—is similar to that seen in amebiasis, with

varying degrees of mucosal invasion, focal necrosis, and ulceration.

Balantidiasis, unlike amebiasis, only rarely spreads hematogenously to

other organs. The diagnosis is made by detection of the trophozoite

stage in stool or sampled colonic tissue. Tetracycline (500 mg four

times daily for 10 days) is an effective therapeutic agent.

Blastocystosis Blastocystis hominis remains an organism of uncertain taxonomy and pathogenicity. Some patients who pass B. hominis

in their stools are asymptomatic, whereas others have diarrhea and

associated intestinal symptoms. Diligent evaluation reveals other

potential bacterial, viral, or protozoal causes of diarrhea in some but

not all patients with symptoms. Because the pathogenicity of B. hominis

is uncertain and because therapy for Blastocystis infection is neither

specific nor uniformly effective, patients with prominent intestinal

symptoms should be fully evaluated for other infectious causes of diarrhea. If diarrheal symptoms associated with Blastocystis are prominent,

either metronidazole (750 mg thrice daily for 10 days) or TMP-SMX

(160 mg/800 mg twice daily for 7 days) can be used.

Dientamoebiasis Dientamoeba fragilis is unique among intestinal

protozoa in that it has a trophozoite stage but not a cyst stage. How trophozoites survive to transmit infection is not known. When symptoms

1768 PART 5 Infectious Diseases

develop in patients with D. fragilis infection, they are generally mild

and include intermittent diarrhea, abdominal pain, and anorexia. The

diagnosis is made by the detection of trophozoites in stool; the lability

of these forms accounts for the greater yield when fecal samples are

preserved immediately after collection. NAATs are more sensitive than

fecal microscopy. Paromomycin (25–35 mg/kg per day in three doses

for 7 days) or metronidazole (500–750 mg three times daily for 10

days) is appropriate for treatment.

TRICHOMONIASIS

Various species of trichomonads can be found in the mouth (in association with periodontitis) and occasionally in the gastrointestinal tract.

Trichomonas vaginalis—one of the most prevalent protozoal parasites

in the United States—is a pathogen of the genitourinary tract and a

major cause of symptomatic vaginitis (Chap. 136).

Life Cycle and Epidemiology T. vaginalis is a pear-shaped,

actively motile organism that measures about 10 × 7 μm, replicates

by binary fission, and inhabits the lower genital tract of females and

the urethra and prostate of males. In the United States, it accounts for

~3 million infections per year in women. While the organism can

survive for a few hours in moist environments and could be acquired

by direct contact, person-to-person venereal transmission accounts for

virtually all cases of trichomoniasis. Its prevalence is greatest among

persons with multiple sexual partners and among those with other

sexually transmitted diseases (Chap. 136).

Clinical Manifestations Many men infected with T. vaginalis are

asymptomatic, although some develop urethritis and a few have epididymitis or prostatitis. In contrast, infection in women, which has an

incubation period of 5–28 days, is usually symptomatic and manifests

with malodorous vaginal discharge (often yellow), vulvar erythema

and itching, dysuria or urinary frequency (in 30–50% of patients), and

dyspareunia. These manifestations, however, do not clearly distinguish

trichomoniasis from other types of infectious vaginitis.

Diagnosis Detection of motile trichomonads by microscopic

examination of wet mounts of vaginal or prostatic secretions has been

the conventional means of diagnosis. Although this approach provides

an immediate diagnosis, its sensitivity for the detection of T. vaginalis

is only ~50–60% in routine evaluations of vaginal secretions. Direct

immunofluorescent antibody staining is more sensitive (70–90%)

than wet-mount examinations. T. vaginalis can be recovered from the

urethra of both males and females and is detectable in males after prostatic massage. NAATs are FDA approved and are highly sensitive and

specific for urine and for endocervical and vaginal swabs from women.

TREATMENT

Trichomoniasis

Metronidazole (either a single 2-g dose or 500-mg doses twice

daily for 7 days) or tinidazole (a single 2-g dose) is effective. All

sexual partners must be treated concurrently to prevent reinfection, especially from asymptomatic males. In males with persistent

symptomatic urethritis after therapy for nongonococcal urethritis, metronidazole therapy should be considered for possible trichomoniasis. Alternatives to metronidazole for treatment during

pregnancy are not readily available. Reinfection often accounts for

apparent treatment failures, but strains of T. vaginalis exhibiting

high-level resistance to metronidazole have been encountered.

Treatment of these resistant infections with higher oral doses,

parenteral doses, or concurrent oral and vaginal doses of metronidazole or with tinidazole has been successful.

■ FURTHER READING

Buret AG et al: Update on Giardia: Highlights from the Seventh International Giardia and Cryptosporidim Conference. Parasite 27:49, 2020.

Carter BL et al: Health sequelae of human cryptosporidiosis in industrialized countries: A systematic review. Parasit Vectors 13:443, 2020.

Coffey CM et al: Evolving epidemiology of reported giardiasis cases in

the United States, 1995-2016. Clin Infect Dis 72:764, 2021.

Han B, Weiss LM: Therapeutic targets for the treatment of microsporidiosis in humans. Expert Opin Ther Targets 22:903, 2018.

Hemphill A et al: Comparative pathobiology of the intestinal protozoan parasites Giardia lamblia, Entamoeba histolytica and Cryptosporidium parvum. Pathogens 8:116, 2019.

Kissinger P: Trichomonas vaginalis: A review of epidemiologic, clinical and treatment issues. BMC Infect Dis 15:307, 2015.

Ramanan P, Pritt BS: Extraintestinal microsporidiosis. J Clin Microbiol

52:3839, 2014.

Van German TO, Muzny CA: Recent advances in the epidemiology,

diagnosis, and management of Trichomonas vaginalis infection.

F1000Res 8:1666, 2019.

Van Gestel RSFE et al: A clinical guideline on Dientamoeba fragilis

infections. Parasitology 146:1131, 2018.

Widmer G et al: Update on Cryptosporidium spp: Highlights from

the Seventh International Giardia and Cryptosporidim Conference.

Parasite 27:14, 2020.

Section 19 Helminthic Infections

230

The word helminth is derived from the Greek helmins (“parasitic

worm”). Helminthic worms are highly prevalent and, depending on

the species, may exist as free-living organisms or as parasites of plant

or animal hosts. The parasitic helminths have co-evolved with specific

mammalian and other host species. Accordingly, most helminthic

infections are restricted to nonhuman hosts, and only rarely do these

zoonotic helminths accidentally cause human infections.

Helminthic parasites of humans belong to two phyla: Nemathelminthes, which includes nematodes (roundworms), and Platyhelminthes, which includes cestodes (tapeworms) and trematodes

(flukes). Helminthic parasites of humans reside within the human

body and hence are the cause of true infections. In contrast, parasites

of other genera that reside only on mucocutaneous surfaces of humans

(e.g., the parasites causing myiasis and scabies) are considered to represent infestations rather than infections.

Helminthic parasites differ substantially from protozoan parasites in

several respects. First, protozoan parasites are unicellular organisms,

whereas helminthic parasites are multicellular worms that possess differentiated organ systems. Second, helminthic parasites have complex

life cycles that require sequential stages of development outside the

human host. Thus, most helminths do not complete their replication

within the human host; rather, they develop to a certain stage within

the mammalian host and, as part of their obligatory life cycle, must

mature further outside that host. During the “extra-human” stages of

their life cycle, helminths exist either as free-living organisms or as

parasites within another host species and thereafter mature into new

developmental stages capable of infecting humans. Thus, with only

two exceptions (Strongyloides stercoralis and Capillaria philippinensis,

which are capable of internal human reinfections), increases in the

number of adult helminths (i.e., the “worm burden”) within the human

Introduction to

Helminthic Infections

Peter F. Weller

1769CHAPTER 230 Introduction to Helminthic Infections

host require repeated exogenous reinfections. In the case of protozoan

parasites, a brief, even singular exposure (e.g., a single mosquito bite

transmitting malaria) may lead rapidly to intense parasite loads and

overwhelming infections; in contrast, for all but the two helminths

noted above, increases in worm burden require multiple and usually

ongoing exposures to infectious forms, such as ingestion of eggs of

intestinal helminths or waterborne exposures to infectious cercariae of

Schistosoma mansoni. This requirement is germane both to the consideration of helminthic infections in individuals and to ongoing global

efforts to interrupt and/or minimize the acquisition of helminthic

infections by humans.

Third, helminthic infections have a predilection toward stimulation

of host immune responses that elicit eosinophilia within human tissues and blood. The many protozoan infections characteristically do

not elicit eosinophilia in infected humans, with only three exceptions

(two intestinal protozoan parasites, Cystoisospora belli and Dientamoeba fragilis, and tissue-borne Sarcocystis species). The magnitude of

helminth-elicited eosinophilia tends to correlate with the extent of tissue

invasion by larvae or adult helminths. For example, in several helminthic infections, including acute schistosomiasis (Katayama syndrome),

paragonimiasis, and hookworm and Ascaris infections, eosinophilia is

most pronounced during the early phases of infection, when migrations of infecting larvae and progression of subsequent developmental

stages through the tissues are greatest. In established infections, local

eosinophilia is often present around helminths in tissues, but blood eosinophilia may be intermittent, mild, or absent. In helminthic infections

in which parasites are well contained within tissues (e.g., echinococcal

cysts) or confined within the lumen of the intestinal tract (e.g., adult

Ascaris or tapeworms), eosinophilia is usually absent.

■ NEMATODES

Nematodes are nonsegmented roundworms. Species of nematodes

are remarkably diverse and abundant in nature. Among the many

thousands of nematode species, few are parasites of humans. Most

nematodes are free-living, and these species have variably evolved to

survive in diverse ecologic niches, including saltwater, freshwater, or

soil. The well-studied organism Caenorhabditis elegans is a free-living

nematode. Nematodes can be either beneficial or deleterious parasites

of plants. Parasitic nematodes have co-evolved with specific mammalian hosts and have no capacity to live their full life cycles in other

hosts. Uncommonly, humans are exposed to infectious stages of nonhuman nematode parasites, and the resultant zoonotic nematode infections can elicit inflammatory and immune responses as larval forms

migrate and die in the unsuitable human host. Examples include pulmonary coin lesions due to mosquito-transmitted infections with the

dog heartworm Dirofilaria immitis; eosinophilic meningoencephalitis

due to ingested eggs of the raccoon ascarid Baylisascaris procyonis; and

eosinophilic meningitis due to ingestion of larvae of the rat lungworm

Angiostrongylus cantonensis.

Nematode parasites of humans include worms that reside in the

intestinal tract or localize in extraintestinal vascular or tissue sites.

Roundworms are bisexual, with separate male and female forms

(except for S. stercoralis, whose adult females are hermaphroditic in the

human intestinal tract). Depending on the species, fertilized females

release either larvae or eggs containing larvae. Nematodes have five

developmental stages: an adult stage and four sequential larval stages.

These parasites characteristically are surrounded by a durable outer

cuticular layer. Nematodes have a nervous system; a muscular system,

including muscle cells under the cuticle; and a developed intestinal

tract, including an oral cavity and an elongated gut that ends in an anal

pore. Adults may range in size from minute to >1 meter in length (with

Dracunculus medinensis, for example, at the long end of this spectrum).

Humans acquire infections with nematode parasites by various

routes, depending on the parasitic species. Ingestion of eggs passed in

human feces is a major global health problem with many of the intestinal

helminths (e.g., Ascaris lumbricoides). In other species, infecting larvae

penetrate skin exposed to fecally contaminated soil (e.g., S. stercoralis,

hookworms) or traverse the skin after the bite of infected insect vectors

(e.g., filariae). Some nematode infections are acquired by consumption

of specific animal-derived foods (e.g., trichinellosis from raw or undercooked pork or wild carnivorous mammals). As noted above, only two

nematodes, S. stercoralis and C. philippinensis, can internally reinfect

humans; thus, for all other nematodes, any increases in worm burden

must be due to continued exogenous reinfections.

■ CESTODES

Tapeworms are the cestode parasites of humans. Adult tapeworms are

elongated, segmented, hermaphroditic flatworms that reside in the

intestinal lumen or, in their larval forms, may live in extraintestinal

tissues. Tapeworms include a head (scolex) and a number of attached

segments (proglottids). The worms attach to the intestinal tract via their

scolices, which may possess suckers, hooks, or grooves. The scolex

is the site of formation of new proglottids. Tapeworms do not have

a functional gut tract; rather, each tapeworm segment passively and

actively obtains nutrients through its specialized surface tegument.

Mature proglottids possess both male and female sex organs, but

insemination usually occurs between adjacent proglottids. Fertilized

proglottids release eggs that are passed in the feces. When ingested by

an intermediate host, an egg releases an oncosphere that penetrates the

gut and develops further in tissues as a cysticercus. Humans acquire

infection by ingesting animal tissues that contain cysticerci, and the

resultant tapeworms develop and reside in the proximal small bowel

(e.g., Taenia solium, T. saginata). Alternatively, if humans ingest eggs of

these cestodes that have been passed in human or animal feces, oncospheres develop and can cause space-occupying extraintestinal cystic

lesions in tissues; examples include cysticercosis due to T. solium and

hydatid disease due to species of Echinococcus.

■ TREMATODES

Trematodes of medical importance include blood flukes, intestinal

flukes, and tissue flukes. Adult flukes are often leaf-shaped flatworms.

Oral and/or ventral suckers help adult flukes maintain their positions

in situ. Flukes have an oral cavity but no distal anal pore. Nutrients

are obtained both through their integument and by ingestion into the

blind intestinal tract. Flukes are hermaphroditic except for blood flukes

(schistosomes), which are bisexual. Eggs are passed in human feces

(Fasciola, Fasciolopsis, Clonorchis, Schistosoma japonicum, S. mansoni),

urine (Schistosoma haematobium), or sputum and feces (Paragonimus).

Expelled eggs release miracidia—usually in water—that infect specific snail species. Within snails, parasites multiply and cercariae are

released. Depending on the species, cercariae can penetrate the skin

(schistosomes) or can develop into metacercariae that can be ingested

with plants (e.g., watercress for Fasciola) or with fish (Clonorchis) or

crabs (Paragonimus).

■ CONCLUSION

Many of the so-called neglected tropical diseases are due to helminthic infections. The health impacts of many helminthic infections

are varied and are based on the frequent need for repeated exposures

to increase the worm burdens in infected humans. In global regions

where exposures to specific helminths occur even in childhood (e.g.,

fecally derived intestinal nematodes, mosquito-transmitted filariae,

or waterborne snail-transmitted schistosomes), the morbidities in

infected individuals can include nutritional, developmental, cognitive, and functional impairments. Ongoing global mass-treatment

programs are currently aimed at diminishing the local prevalences of

specific helminths and their consequent impacts on the health of local

populations.

1770 PART 5 Infectious Diseases

Nematodes are elongated, symmetric roundworms. Parasitic nematodes of medical significance may be broadly classified as either predominantly intestinal or tissue nematodes. The intestinal nematodes

are covered in Chap. 232. This chapter covers the tissue nematodes

that cause trichinellosis, visceral and ocular larva migrans, cutaneous

larva migrans, cerebral angiostrongyliasis, and gnathostomiasis. All of

these zoonotic infections result from incidental exposure to infectious

nematodes. The clinical symptoms of these infections are due largely

to invasive larval stages that (except in the case of Trichinella) do not

reach maturity in humans.

■ TRICHINELLOSIS

Trichinellosis develops after the ingestion of meat containing cysts of

Trichinella (e.g., pork or other meat from a carnivore). Although most

infections are mild and asymptomatic, heavy infections can cause

severe enteritis, periorbital edema, myositis, and (infrequently) death.

Life Cycle and Epidemiology Nine species of Trichinella and

13 genotypes are recognized as causes of infection in humans. Two

species are distributed worldwide: T. spiralis, which is found in a great

variety of carnivorous and omnivorous animals, and T. pseudospiralis,

which is found in mammals and birds. T. nativa is present in Arctic

and subarctic regions and infects bears, foxes, and walruses; T. nelsoni

is found in equatorial eastern Africa, where it is common among felid

predators and scavengers such as hyenas and bush pigs; and T. britovi

is found in Europe, western Africa, and western Asia among carnivores

but not among domestic swine. T. murrelli is

present in wild animals in North American and

Japan. T. papuae is found in Papua New Guinea,

Thailand, Taiwan, and Cambodia in domestic

and feral pigs and in saltwater crocodiles and

turtles. T. zimbabwensis is present in crocodiles

in Tanzania. T. patagoniensis is found in cougars

in South America.

After human consumption of trichinous

meat, encysted larvae are liberated by digestive

acid and proteases (Fig. 231-1). The larvae

invade the small-bowel mucosa and mature

into adult worms. After ~1 week, female worms

release newborn larvae that migrate via the

circulation to striated muscle. The larvae of all

species except T. pseudospiralis, T. papuae, and

T. zimbabwensis then encyst by inducing a radical transformation in the muscle cell architecture. Host immune responses may help to expel

intestinal adult worms but have few deleterious

effects on muscle-dwelling larvae.

Human trichinellosis classically has been

caused by the ingestion of infected pork products and thus can occur in almost any location

where the meat of domestic or wild swine is

eaten. Increasingly, human trichinellosis has

also been acquired from the meat of other

animals, including dogs (in parts of Asia and

Africa), horses (in Italy and France), and bears

and walruses (in northern regions). Although

cattle (being herbivores) are not natural hosts

of Trichinella, beef has been implicated in outbreaks when contaminated or adulterated with

231

trichinous pork. About 12 cases of trichinellosis are reported annually

in the United States, but most mild cases probably remain undiagnosed.

Recent U.S. and Canadian outbreaks have been attributable predominantly to consumption of wild game (especially bear and walrus meat).

Pathogenesis and Clinical Features Clinical symptoms of trichinellosis arise from the successive phases of parasite enteric invasion,

larval migration, and muscle encystment (Fig. 231-1). Most light infections (those with <10 larvae per gram of muscle) are asymptomatic,

whereas heavy infections (which can involve >50 larvae per gram of

muscle) can be life-threatening. An initial enteric phase due to release

of ingested muscle larvae may elicit diarrhea, abdominal pain, constipation, and nausea during the first weeks after infection.

Symptoms due to larval migration and muscle invasion begin to

appear in the second week after infection. The migrating Trichinella larvae provoke a marked local and systemic hypersensitivity reaction, with

fever and eosinophilia. Periorbital and facial edema is common, as are

hemorrhages in the subconjunctivae, retina, and nail beds (“splinter”

hemorrhages). A maculopapular rash, headache, cough, dyspnea, or

dysphagia sometimes develops. Myocarditis with tachyarrhythmias or

heart failure—and, less commonly, encephalitis or pneumonitis—may

develop and accounts for most deaths of patients with trichinellosis.

Upon onset of larval encystment in muscle 2–3 weeks after infection, symptoms of myositis with myalgias, muscle edema, and weakness develop, usually overlapping with the inflammatory reactions

to migrating larvae. The most commonly involved muscle groups

include the extraocular muscles; the biceps; and the muscles of the jaw,

neck, lower back, and diaphragm. Peaking ~3 weeks after infection,

symptoms subside only gradually during a prolonged convalescence.

Uncommon infections with T. pseudospiralis, whose larvae do not

encapsulate in muscles, elicit a prolonged polymyositis-like illness.

Laboratory Findings and Diagnosis Blood eosinophilia develops in >90% of patients with symptomatic trichinellosis and may

peak at a level of >50% 2–4 weeks after infection. Serum levels of

muscle enzymes, including creatine phosphokinase, are elevated in

most symptomatic patients. Patients should be questioned thoroughly

Trichinellosis and

Other Tissue Nematode

Infections

Peter F. Weller

Larvae are released

in the stomach and mature

into adults over 1–2 wks

in the small bowel,

causing:

Larvae migrate,

penetrate striated

muscle, reside in

"nurse-cells," and encyst,*

causing:

Muscle pain, fever,

periorbital edema,

eosinophilia, occasional

CNS or cardiac damage

Encysted larvae ingested

in undercooked pork,

boar, horse, or bear

Irritation and mild abdominal

cramping or even diarrhea

*T. papuae, T. zimbabwensis, and T. pseudospiralis do not encyst.

Similar cycle (as humans)

in swine or other carnivores

(rats, bears, foxes, dogs, or horses)

FIGURE 231-1 Life cycle of Trichinella spiralis (cosmopolitan); nelsoni (equatorial Africa); britovi (Europe,

western Africa, western Asia); nativa (Arctic); murrelli (North America); papuae (Papua New Guinea);

zimbabwensis (Tanzania); and pseudospiralis (cosmopolitan). CNS, central nervous system. (Reproduced with

permission from RL Guerrant et al [eds]: Tropical Infectious Diseases: Principles, Pathogens and Practice,

2nd ed, Elsevier, 2006.)

1771CHAPTER 231 Trichinellosis and Other Tissue Nematode Infections

about their consumption of pork or wild animal meat and about illness

in other individuals who ate the same meat. A presumptive clinical

diagnosis can be based on fevers, eosinophilia, periorbital edema, and

myalgias after a suspect meal. A rise in the titer of parasite-specific

antibody, which usually does not occur until after the third week of

infection, confirms the diagnosis. Alternatively, a definitive diagnosis

requires surgical biopsy of at least 1 g of involved muscle; the yields

are highest near tendon insertions. The fresh muscle tissue should

be compressed between glass slides and examined microscopically

(Fig. 231-2) because larvae may be missed by examination of routine

histopathologic sections alone.

TREATMENT

Trichinellosis

Most lightly infected patients recover uneventfully with bed rest,

antipyretics, and analgesics. Glucocorticoids like prednisone

(Table 231-1) are beneficial for severe myositis and myocarditis.

Mebendazole and albendazole are active against enteric stages of

the parasite, but their efficacy against encysted larvae has not been

conclusively demonstrated.

Prevention Larvae are usually killed by cooking pork until it is no

longer pink or by freezing it at −15°C for 3 weeks. However, Arctic

T. nativa larvae in walrus or bear meat are relatively resistant and may

remain viable despite freezing.

■ VISCERAL AND OCULAR LARVA MIGRANS

Visceral larva migrans is a syndrome caused by nematodes that are

normally parasitic for nonhuman host species. In humans, these

nematode larvae do not develop into adult worms but instead migrate

through host tissues and elicit eosinophilic inflammation. The most

common form of visceral larva migrans is toxocariasis due to larvae of

the canine ascarid Toxocara canis; the syndrome is due less commonly

to the feline ascarid T. cati and even less commonly to the pig ascarid

Ascaris suum. Rare cases with eosinophilic meningoencephalitis have

been caused by the raccoon ascarid Baylisascaris procyonis.

Life Cycle and Epidemiology The canine roundworm T. canis

is distributed among dogs worldwide. Ingestion of infective eggs by

dogs is followed by liberation of Toxocara larvae, which penetrate

the gut wall and migrate intravascularly into canine tissues, where

most remain in a developmentally arrested state. During pregnancy,

some larvae resume migration in bitches and infect puppies prenatally (through transplacental transmission) or after birth (through

suckling). Thus, in lactating bitches and puppies, larvae return to the

intestinal tract and develop into adult worms, which produce eggs that

are released in the feces. Eggs must undergo embryonation over several

weeks to become infectious. Humans acquire toxocariasis mainly by

eating soil contaminated by puppy feces that contains infective T. canis

eggs. Visceral larva migrans is most common among children who

habitually eat dirt.

Pathogenesis and Clinical Features Clinical disease most commonly afflicts preschool children. After humans ingest Toxocara eggs,

the larvae hatch and penetrate the intestinal mucosa, from which they

are carried by the circulation to a wide variety of organs and tissues. The

larvae invade the liver, lungs, central nervous system (CNS), and other

sites, provoking intense local eosinophilic granulomatous responses.

The degree of clinical illness depends on larval number and tissue

distribution, reinfection, and host immune responses. Most light infections are asymptomatic and may be evidenced only by blood eosinophilia. Characteristic symptoms of visceral larva migrans include fever,

malaise, anorexia and weight loss, cough, wheezing, and rashes. Hepatosplenomegaly is common. These features may be accompanied by

extraordinary peripheral eosinophilia at levels that may approach 90%.

Uncommonly, seizures or behavioral disorders develop. Rare deaths are

due to severe neurologic, pneumonic, or myocardial involvement.

The ocular form of the larva migrans syndrome occurs when

Toxocara larvae invade the eye. An eosinophilic granulomatous mass,

most commonly in the posterior pole of the retina, develops around

the entrapped larva. The retinal lesion can mimic retinoblastoma

in appearance, and mistaken diagnosis of the latter condition can

lead to unnecessary enucleation. The spectrum of eye involvement

also includes endophthalmitis, uveitis, and chorioretinitis. Unilateral

visual disturbances, strabismus, and eye pain are the most common

presenting symptoms. In contrast to visceral larva migrans, ocular

toxocariasis usually develops in older children or young adults with

no history of pica; these patients seldom have eosinophilia or visceral

manifestations.

Diagnosis In addition to eosinophilia, leukocytosis and hypergammaglobulinemia may be evident. Transient pulmonary infiltrates are

apparent on chest x-rays of about one-half of patients with symptoms

of pneumonitis. The clinical diagnosis can be confirmed by an enzymelinked immunosorbent assay for toxocaral antibodies. Stool examination for parasite eggs is worthless in toxocariasis, since the larvae do

not develop into egg-producing adults in humans.

FIGURE 231-2 Trichinella larva encysted in a characteristic hyalinized capsule

in striated muscle tissue. (Photographs provided by Dr. Mary Wu Chang with

permission of patient’s mother.)

TABLE 231-1 Therapy for Tissue Nematode Infections

INFECTION SEVERITY TREATMENT

Trichinellosis Mild Supportive

Moderate Albendazole (400 mg bid × 8–14 days)

or

Mebendazole (200–400 mg tid × 3 days,

then 500 mg tid × 10 days)

Severe Add glucocorticoids (e.g., prednisone,

1 mg/kg qd × 5 days)

Visceral larva

migrans

Mild to

moderate

Supportive

Severe Glucocorticoids (as above)

Ocular Not fully defined; albendazole (800 mg

bid for adults, 400 mg bid for children)

with glucocorticoids × 5–20 days has

been effective

Cutaneous larva

migrans

Ivermectin (single dose, 200 μg/kg) or

Albendazole (200 mg bid × 3 days)

Angiostrongyliasis Mild to

moderate

Supportive

Severe Glucocorticoids (as above)

Gnathostomiasis Ivermectin (200 μg/kg per day ×

2 days) or

Albendazole (400 mg bid × 21 days)

1772 PART 5 Infectious Diseases

Eosinophilic meningitis

2 weeks

3rd-stage larvae (consumed

in snail or slime) penetrate gut,

go to CNS (then lung in rat)

Larvae consumed by land

snail/slug (Achatina fulica)

viable in fresh water

Adult in pulmonary artery

produces fertile eggs; larvae

hatch, penetrate arterioles,

migrate up bronchi, and are

coughed up, swallowed, and

passed in feces

FIGURE 231-3 Life cycle of Angiostrongylus cantonensis (rat lung worm) found in Southeast Asia and the Pacific Basin as well as on Caribbean islands, in countries of

Central and South America, and in the southern United States. CNS, central nervous system. (Reproduced with permission from RL Guerrant et al [eds]: Tropical Infectious

Diseases: Principles, Pathogens and Practice, 2nd ed, Elsevier, 2006.)

TREATMENT

Visceral and Ocular Larva Migrans

The vast majority of Toxocara infections are self-limited and resolve

without specific therapy. In patients with severe myocardial, CNS,

or pulmonary involvement, glucocorticoids may be employed to

reduce inflammatory complications. Available anthelmintic drugs,

including mebendazole and albendazole, have not been shown

conclusively to alter the course of larva migrans. Control measures

include prohibiting dog excreta in public parks and playgrounds,

deworming dogs, and preventing pica in children. Treatment of

ocular disease is not fully defined, but the administration of

albendazole in conjunction with glucocorticoids has been effective

(Table 231-1).

■ CUTANEOUS LARVA MIGRANS

Cutaneous larva migrans (“creeping eruption”) is a serpiginous skin

eruption caused by burrowing larvae of animal hookworms, usually

the dog and cat hookworm Ancylostoma braziliense. The larvae hatch

from eggs passed in dog and cat feces and mature in the soil. Humans

become infected after skin contact with soil in areas frequented by dogs

and cats. Cutaneous larva migrans is prevalent among children and

travelers in regions with warm humid climates, including the southeastern United States.

After larvae penetrate the skin, erythematous lesions form along

the tortuous tracks of their migration through the dermal-epidermal

junction; the larvae advance several centimeters in a day. The intensely

pruritic lesions may occur anywhere on the body and can be numerous

if the patient has lain on the ground. Vesicles and bullae may form later.

The animal hookworm larvae do not mature in humans and, without

treatment, will die after an interval ranging from weeks to a couple of

months, with resolution of skin lesions. The diagnosis is made on clinical grounds. Skin biopsies only rarely detect diagnostic larvae. Symptoms can be alleviated by ivermectin or albendazole (Table 231-1).

■ ANGIOSTRONGYLIASIS

Angiostrongylus cantonensis, the rat lungworm, is the most common

cause of human eosinophilic meningitis (Fig. 231-3).

Life Cycle and Epidemiology This infection occurs principally

in Southeast Asia and the Pacific Basin but has spread to other areas

of the world, including the Caribbean islands, countries in Central and

South America, and the southern United States. A. cantonensis larvae

produced by adult worms in the rat lung migrate to the gastrointestinal

tract and are expelled with the feces. They develop into infective larvae

in land snails and slugs. Humans acquire the infection by ingesting raw

infected mollusks; vegetables contaminated by mollusk slime; or crabs,

freshwater shrimp, and certain marine fish that have themselves eaten

infected mollusks. The larvae then migrate to the brain.

Pathogenesis and Clinical Features The parasites eventually

die in the CNS, but not before initiating pathologic consequences that,

in heavy infections, can result in permanent neurologic sequelae or

death. Migrating larvae cause marked local eosinophilic inflammation

and hemorrhage, with subsequent necrosis and granuloma formation

around dying worms. Clinical symptoms develop 2–35 days after the

ingestion of larvae. Patients usually present with an insidious or abrupt

excruciating frontal, occipital, or bitemporal headache. Neck stiffness,

nausea and vomiting, and paresthesias are also common. Fever, cranial

and extraocular nerve palsies, seizures, paralysis, and lethargy are

uncommon.

Laboratory Findings Examination of cerebrospinal fluid (CSF) is

mandatory in suspected cases and usually reveals an elevated opening

pressure, a white blood cell count of 150–2000/μL, and an eosinophilic

pleocytosis of >20%. The protein concentration is usually elevated and

the glucose level normal. The larvae of A. cantonensis are only rarely

seen in CSF. Peripheral-blood eosinophilia may be mild. The diagnosis

is generally based on the clinical presentation of eosinophilic meningitis together with a compatible epidemiologic history.

TREATMENT

Angiostrongyliasis

Specific chemotherapy is not of benefit in angiostrongyliasis; larvicidal agents may exacerbate inflammatory brain lesions. Management consists of supportive measures, including the administration

of analgesics, sedatives, and—in severe cases—glucocorticoids

(Table 231-1). Repeated lumbar punctures with removal of CSF

can relieve symptoms. In most patients, cerebral angiostrongyliasis

has a self-limited course, and recovery is complete. The infection

may be prevented by adequately cooking snails, crabs, and prawns

and inspecting vegetables for mollusk infestation. Other parasitic

or fungal causes of eosinophilic meningitis in endemic areas may

1773CHAPTER 232 Intestinal Nematode Infections

More than a billion persons worldwide are infected with one or more

species of intestinal nematodes. Table 232-1 summarizes biologic

and clinical features of infections due to the major intestinal parasitic

nematodes. These parasites are most common in regions with poor

fecal sanitation, particularly in resource-poor countries in the tropics

and subtropics, but they have also been seen with increasing frequency

among immigrants and refugees to resource-rich countries. Although

nematode infections are not usually fatal, they contribute to malnutrition and diminished work capacity. It is interesting that these helminth infections may protect some individuals from allergic disease.

Humans may on occasion be infected with nematode parasites that

ordinarily infect animals; these zoonotic infections produce diseases

such as trichostrongyliasis, anisakiasis, capillariasis, and abdominal

angiostrongyliasis.

Intestinal nematodes are roundworms; they range in length from

1 mm to many centimeters when mature (Table 232-1). Their life cycles

are complex and highly varied; some species, including Strongyloides

stercoralis and Enterobius vermicularis, can be transmitted directly

from person to person, while others, such as Ascaris lumbricoides and

the hookworms, require a soil phase for development. Because most

helminth parasites do not self-replicate, the acquisition of a heavy

burden of adult worms requires repeated exposure to the parasite in

its infectious stage, whether larva or egg. Hence, clinical disease, as

opposed to asymptomatic (or subclinical) infection, generally develops only with prolonged exposure in an endemic area and is typically

related to infection intensity. In persons with marginal nutrition, intestinal helminth infections may impair growth and development. Eosinophilia and elevated serum IgE levels are features of many helminth

infections and, when unexplained, should always prompt a search

for intestinal helminths. Significant protective immunity to intestinal nematodes appears not to develop in humans, although the host

immune response to these infections has not been elucidated in detail.

■ ASCARIASIS

A. lumbricoides is the largest intestinal nematode parasite of humans,

reaching up to 40 cm in length. Most infected individuals have low worm

burdens and are asymptomatic. Clinical disease arises from larval migration in the lungs or effects of the adult worms in the intestines.

Life Cycle Adult worms live in the lumen of the small intestine.

Mature female Ascaris worms are extraordinarily fecund, each producing up to 240,000 eggs a day that pass with the feces. Ascarid eggs,

which are remarkably resistant to environmental stresses, become

infective after several weeks of maturation in the soil and can remain

infective for years. After infective eggs are swallowed, larvae hatched in

the intestine invade the mucosa, migrate through the circulation to the

lungs, break into the alveoli, ascend the bronchial tree, and return—

through swallowing—to the small intestine, where they develop into

adult worms. The time between initial infection and egg production is

typically between 2–3 months. Adult worms live for 1–2 years.

Epidemiology Ascaris is widely distributed in tropical and subtropical regions as well as in other humid areas in more temperate

regions of the world. Transmission typically occurs through fecally

contaminated soil and is due either to a lack of sanitary facilities or to

the use of human feces as fertilizer. With their propensity for hand-tomouth fecal carriage, younger children are most often affected. Infection outside endemic areas, though uncommon, can occur when eggs

on transported vegetables are ingested.

Clinical Features During the lung phase of larval migration,

~9–12 days after egg ingestion, patients may develop an irritating

232 Intestinal Nematode

Infections

Thomas B. Nutman, Peter F. Weller

include gnathostomiasis (see below), paragonimiasis (Chap. 234),

schistosomiasis (Chap. 234), neurocysticercosis (Chap. 235), and

coccidioidomycosis (Chap. 213).

■ GNATHOSTOMIASIS

Infection of human tissues with larvae of Gnathostoma spinigerum can

cause eosinophilic meningoencephalitis, migratory cutaneous swellings, or invasive masses of the eye and visceral organs.

Life Cycle and Epidemiology Human gnathostomiasis occurs

in many countries and is notably endemic in Southeast Asia and parts

of China and Japan. In nature, the mature adult worms parasitize the

gastrointestinal tract of dogs and cats. First-stage larvae hatch from

eggs passed into water and are ingested by Cyclops species (water fleas).

Infective third-stage larvae develop in the flesh of many animal species

(including fish, frogs, eels, snakes, chickens, and ducks) that have eaten

either infected Cyclops or another infected second intermediate host.

Humans typically acquire the infection by eating raw or undercooked

fish or poultry. Raw fish dishes, such as som fak in Thailand and

sashimi in Japan, account for many cases of human gnathostomiasis.

Some cases in Thailand result from the local practice of applying frog

or snake flesh as a poultice.

Pathogenesis and Clinical Features Clinical symptoms are due

to the aberrant migration of a single larva into cutaneous, visceral,

neural, or ocular tissues. After invasion, larval migration may cause

local inflammation, with pain, cough, or hematuria accompanied by

fever and eosinophilia. Painful, itchy, migratory swellings may develop

in the skin, particularly in the distal extremities or periorbital area.

Cutaneous swellings usually last ~1 week but often recur intermittently

over many years. Larval invasion of the eye can provoke a sight-threatening inflammatory response. Invasion of the CNS results in eosinophilic meningitis with myeloencephalitis, a serious complication

due to ascending larval migration along a large nerve tract. Patients

characteristically present with agonizing radicular pain and paresthesias in the trunk or a limb, which are followed shortly by paraplegia.

Cerebral involvement, with focal hemorrhages and tissue destruction,

is often fatal.

Diagnosis and Treatment Cutaneous migratory swellings with

marked peripheral eosinophilia, supported by an appropriate geographic and dietary history, generally constitute an adequate basis for

a clinical diagnosis of gnathostomiasis. However, patients may present

with ocular or cerebrospinal involvement without antecedent cutaneous swellings. In the latter case, eosinophilic pleocytosis is demonstrable (usually along with hemorrhagic or xanthochromic CSF), but

worms are almost never recovered from CSF. Surgical removal of the

parasite from subcutaneous or ocular tissue, though rarely feasible, is

both diagnostic and therapeutic. Albendazole or ivermectin may be

helpful (Table 231-1). At present, cerebrospinal involvement is managed with supportive measures and generally with a course of glucocorticoids. Gnathostomiasis can be prevented by adequate cooking of

fish and poultry in endemic areas.

■ FURTHER READING

Centers for Disease Control and Prevention: Surveillance for

trichinellosis—United States, 2015, Annual Summary. Atlanta, GA:

U.S. Department of Health and Human Services, CDC, 2017.

Lupi O et al: Mucocutaneous manifestations of helminth infections.

Nematodes. J Am Acad Dermatol 73:929, 2015.

Martins YC et al: Central nervous system manifestations of Angiostrongylus cantonensis infection. Acta Trop 141:46, 2015.

Rostami A et al: Meat sources of infection for outbreaks of human

trichinellosis. Food Microbiol 64:65, 2017.

Rostami A et al: Human toxocariasis—A look at a neglected disease

through an epidemiological “prism.” Infect Genet Evol 74:104002,

2019.

Sitcar AD et al: Raccoon roundworm infection associated with

central nervous system disease and ocular disease—six states,

2013–2015. Morbid Mortal Wkly Rep 65:930, 2016.

1774 PART 5 Infectious Diseases

TABLE 232-1 Major Human Intestinal Parasitic Nematodes

FEATURE

PARASITIC NEMATODE

ASCARIS LUMBRICOIDES

(ROUNDWORM)

NECATOR AMERICANUS,

ANCYLOSTOMA

DUODENALE,

ANCYLOSTOMA

CEYLANICUM (HOOKWORM)

STRONGYLOIDES

STERCORALIS

TRICHURIS

TRICHIURA

(WHIPWORM)

ENTEROBIUS

VERMICULARIS

(PINWORM)

Global prevalence in

humans (millions)

807 576 100 604 209

Endemic areas Worldwide Hot, humid regions Hot, humid regions Worldwide Worldwide

Infective stage Egg Filariform larva Filariform larva Egg Egg

Route of infection Oral Percutaneous Percutaneous or

autoinfective

Oral Oral

Gastrointestinal location

of worms

Jejunal lumen Jejunal mucosa Small-bowel mucosa Cecum, colonic

mucosa

Cecum, appendix

Adult worm size 15–40 cm 7–12 mm 2 mm 30–50 mm 8–13 mm (female)

Pulmonary passage of

larvae

Yes Yes Yes No No

Incubation perioda

 (days) 60–75 40–100 17–28 70–90 35–45

Longevity 1 year N. americanus: 2–5 years

A. duodenale: 6–8 years

A. ceylanicum: 6–8 yearsb

Decades (owing to

autoinfection)

5 years 2 months

Fecundity (eggs/day/

worm)

240,000 N. americanus: 4000–10,000

A. duodenale: 10,000–25,000

A. ceylanicum: 5,000–15,000

5000–10,000 3000–7000 2000

Principal symptoms Rarely, biliary obstruction

or, in heavy infections,

gastrointestinal

obstruction

Iron-deficiency anemia in

heavy infection

Gastrointestinal

symptoms; malabsorption

or sepsis in hyperinfection

Gastrointestinal

symptoms or anemia

in heavy infection

Perianal pruritus

Diagnostic stage Eggs in stool Eggs in fresh stool, larvae in

old stool

Larvae in stool or

duodenal aspirate;

sputum in hyperinfection

Eggs in stool Eggs from perianal skin

on cellulose acetate tape

Treatment Mebendazole

Albendazole

Ivermectin

Mebendazole

Albendazole

Ivermectin

Albendazole

Mebendazole

Albendazole

Ivermectin

Mebendazole

Albendazole

a

Time from infection to egg production by mature female worm. b

Assumed but no evidence base in humans.

nonproductive cough and burning substernal discomfort that is aggravated by coughing or deep inspiration. Dyspnea and blood-tinged sputum are less common. Fever can occur. Eosinophilia develops during

this symptomatic phase and subsides slowly over weeks. Chest imaging

may reveal evidence of eosinophilic pneumonitis (Löffler’s syndrome),

with rounded infiltrates a few millimeters to several centimeters in

size. These infiltrates may be transient and intermittent, clearing after

several weeks. Where there is seasonal transmission of the parasite,

seasonal pneumonitis with eosinophilia may develop in previously

infected and sensitized hosts.

In established infections, adult worms in the small intestine usually cause no symptoms. In heavy infections, particularly in children,

a large bolus of entangled worms can cause pain and small-bowel

obstruction, sometimes complicated by perforation, intussusception,

or volvulus. Single worms may cause disease when they migrate into

aberrant sites. A large worm can enter and occlude the biliary tree,

causing biliary colic, cholecystitis, cholangitis, pancreatitis, or (rarely)

intrahepatic abscesses. Migration of an adult worm up the esophagus

can provoke coughing and oral expulsion of the worm. In highly

endemic areas, intestinal and biliary ascariasis can rival acute appendicitis and gallstones as causes of surgical acute abdomen.

Laboratory Findings Most cases of ascariasis can be diagnosed

by microscopic detection of characteristic Ascaris eggs (65 × 45 μm)

in fecal samples, although increasingly, polymerase chain reaction

(PCR) of DNA extracted from stool is being used in research and

some clinical settings. Occasionally, patients present after passing an

adult worm—identifiable by its large size and smooth cream-colored

surface—in the stool or, much less commonly, through the mouth

or nose. During the early transpulmonary migratory phase, when

eosinophilic pneumonitis occurs, larvae can be found in sputum or

gastric aspirates before diagnostic eggs appear in the stool. The eosinophilia that is prominent during this early stage usually decreases to

minimal levels in established infection. Adult worms may be visualized, occasionally serendipitously, on contrast studies of the gastrointestinal tract. A plain abdominal film may reveal masses of worms in

gas-filled loops of bowel in patients with intestinal obstruction. Pancreaticobiliary worms can be detected by ultrasound and endoscopic

retrograde cholangiopancreatography; the latter method also has been

used to extract biliary Ascaris worms.

TREATMENT

Ascariasis

Ascariasis should always be treated to prevent potentially serious

complications. Albendazole (400 mg once), mebendazole (100 mg

twice daily for 3 days or 500 mg once), or ivermectin (150–200 μg/

kg once) is effective. These medications are contraindicated in pregnancy, however. Mild diarrhea and abdominal pain are uncommon

side effects of these agents. Partial intestinal obstruction should be

managed with nasogastric suction, IV fluid administration, and

instillation of piperazine through the nasogastric tube, but complete

obstruction and its severe complications require immediate surgical

intervention.

■ HOOKWORM

Three species (Ancylostoma duodenale, Ancylostoma ceylanicum, and

Necator americanus) are responsible for most human hookworm infections. Most infected individuals are asymptomatic. Hookworm disease

1775CHAPTER 232 Intestinal Nematode Infections

develops from a combination of factors—a heavy worm burden, a

prolonged duration of infection, and an inadequate iron intake—and

results in iron-deficiency anemia and, on occasion, hypoproteinemia.

Life Cycle Adult hookworms, which are ~1 cm long, use buccal teeth

(Ancylostoma) or cutting plates (Necator) to attach to the small-bowel

mucosa and suck blood (0.2 mL/d per Ancylostoma adult) and interstitial fluid. The adult hookworms produce thousands of eggs daily. The

eggs are deposited with feces in soil, where rhabditiform larvae hatch

and develop over a 1-week period into infectious filariform larvae.

Infective larvae penetrate the skin and reach the lungs by way of the

bloodstream. There they invade alveoli and ascend the airways before

being swallowed and reaching the small intestine. The prepatent period

from skin invasion to appearance of eggs in the feces is ~6–8 weeks,

but it may be longer with Ancylostoma spp. Larvae of Ancylostoma spp.,

if swallowed, can survive and develop directly in the intestinal mucosa.

Adult hookworms may survive over a decade but usually live ~6–8 years

for A. duodenale and 2–5 years for N. americanus.

Epidemiology A. duodenale is prevalent in southern Europe,

North Africa, and northern Asia, and N. americanus is the predominant species in the Western Hemisphere and equatorial Africa.

A. ceylanicum is most prevalent in Southeast Asia. The species can

overlap geographically, particularly in Southeast Asia. Age prevalence

studies have shown a constant increase in hookworm prevalence over

time; older children have the greatest intensity of hookworm infection;

however, in rural areas where fields are fertilized with human feces,

older working adults also may be heavily infected.

Clinical Features Most hookworm infections are clinically asymptomatic. Infective larvae may provoke pruritic maculopapular dermatitis

(“ground itch”) at the site of skin penetration as well as serpiginous tracks

of subcutaneous migration (similar to those of cutaneous larva migrans;

Chap. 231) in previously sensitized hosts. Larvae migrating through the

lungs occasionally cause mild transient pneumonitis, but this condition

develops less frequently in hookworm infection than in ascariasis. In

the early intestinal phase, infected persons may develop epigastric pain

(often with postprandial accentuation), inflammatory diarrhea, or other

abdominal symptoms accompanied by eosinophilia. The major consequence of chronic hookworm infection is iron deficiency. Symptoms are

minimal if iron intake is adequate, but marginally nourished individuals

develop symptoms of progressive iron-deficiency anemia and hypoproteinemia, including weakness and shortness of breath.

Laboratory Findings The diagnosis is established by the finding of characteristic 40- by 60-μm oval hookworm eggs in the

feces. Stool-concentration procedures may be required to detect light

infections. Eggs of the three species are indistinguishable by light

microscopy, whereas PCR has provided a significant improvement

in species-specific diagnosis. In a stool sample that is not fresh, the

eggs may have hatched to release rhabditiform larvae, which need to

be differentiated from those of S. stercoralis. Hypochromic microcytic

anemia, occasionally with eosinophilia or hypoalbuminemia, is characteristic of hookworm disease.

TREATMENT

Hookworm Infection

Hookworm infection can be treated with several safe and highly

effective anthelmintic drugs, including albendazole (400 mg once)

and mebendazole (500 mg once). Mild iron-deficiency anemia can

often be treated with oral iron alone. Severe hookworm disease with

protein loss and malabsorption necessitates nutritional support and

oral iron replacement along with deworming. There is significant

concern that the benzimidazoles (mebendazole and albendazole)

are becoming much less effective against human hookworms.

Ancylostoma caninum and Ancylostoma braziliense A. caninum,

the canine hookworm, has been identified as a cause of human eosinophilic enteritis, especially in northeastern Australia. In this zoonotic

infection, adult hookworms attach to the small intestine (where they

may be visualized by endoscopy) and elicit abdominal pain and

intense local eosinophilia. Treatment with mebendazole (100 mg

twice daily for 3 days) or albendazole (400 mg once) or endoscopic

removal is effective. Both of these animal hookworm species can cause

cutaneous larva migrans (“creeping eruption”; Chap. 231).

■ STRONGYLOIDIASIS

S. stercoralis is distinguished by its ability—unique among helminths

(except for Capillaria; see below)—to replicate in the human host. This

capacity permits ongoing cycles of autoinfection as infective larvae are

internally produced. Infection with S. stercoralis can thus persist for

decades without further exposure of the host to exogenous infective

larvae. In immunocompromised hosts, large numbers of invasive

Strongyloides larvae can disseminate widely and can be fatal.

Life Cycle In addition to a parasitic cycle of development, Strongyloides can undergo a free-living cycle of development in the soil

(Fig. 232-1). This adaptability facilitates the parasite’s survival in the

absence of mammalian hosts. Rhabditiform larvae passed in feces can

transform into infectious filariform larvae either directly or after a

free-living phase of development. Humans acquire S. stercoralis when

filariform larvae in fecally contaminated soil penetrate the skin or

mucous membranes. The larvae then travel through the bloodstream

to the lungs, where they break into the alveolar spaces, ascend the

bronchial tree, are swallowed, and thereby reach the small intestine.

There the larvae mature into adult worms that penetrate the mucosa

of the proximal small bowel. The minute (2-mm-long) parasitic adult

female worms reproduce by parthenogenesis; adult males do not exist.

Eggs hatch in the intestinal mucosa, releasing rhabditiform larvae that

migrate to the lumen and pass with the feces into soil. Alternatively,

rhabditiform larvae in the bowel can develop directly into filariform

larvae that penetrate the colonic wall or perianal skin and enter the

circulation to repeat the migration that establishes ongoing internal

reinfection. This autoinfection cycle allows strongyloidiasis to persist

for decades.

Epidemiology S. stercoralis is spottily distributed in tropical areas

and other hot, humid regions and is particularly common in Southeast

Asia, sub-Saharan Africa, and Brazil. In the United States, the parasite

is endemic in parts of the Southeast and is found in immigrants, refugees, travelers, and military personnel who have lived in endemic areas.

Clinical Features In uncomplicated strongyloidiasis, many

patients are asymptomatic or have mild cutaneous and/or abdominal

symptoms. Recurrent urticaria, often involving the buttocks and wrists,

is the most common cutaneous manifestation. Migrating larvae can

elicit a pathognomonic serpiginous eruption, larva currens (“running

larva”). This pruritic, raised, erythematous lesion advances as rapidly

as 10 cm/h along the course of larval migration. Adult parasites burrow

into the duodenojejunal mucosa and can cause abdominal (usually

midepigastric) pain, which resembles peptic ulcer pain except that

it is aggravated by food ingestion. Nausea, diarrhea, gastrointestinal

bleeding, mild chronic colitis, and weight loss can occur. Small-bowel

obstruction may develop with early, heavy infection. Pulmonary

symptoms are rare in uncomplicated strongyloidiasis. Eosinophilia is

common, with levels fluctuating over time.

The ongoing autoinfection cycle of S. stercoralis is normally constrained by unknown factors of the host’s immune system. Abrogation

of host immunity, especially with glucocorticoid therapy and much

less commonly with other immunosuppressive medications, leads to

hyperinfection, with the generation of large numbers of filariform larvae. Colitis, enteritis, or malabsorption may develop. In disseminated

strongyloidiasis, larvae may invade not only gastrointestinal tissues and

the lungs but also the central nervous system, peritoneum, liver, and

kidneys. Moreover, bacteremia may develop because of the passage of

enteric flora through disrupted mucosal barriers. Gram-negative sepsis, pneumonia, or meningitis may complicate or dominate the clinical

course. Eosinophilia is often absent in severely infected patients. Disseminated strongyloidiasis, particularly in patients with unsuspected

1776 PART 5 Infectious Diseases

2-mm hermaphroditic

adult s

penetrate small-bowel

mucosa and release eggs,

which hatch to

rhabditiform larvae.

Larvae shed in stool

Lung or intestinal stage may cause:

Free-living

1-mm adults

in soil

Eggs in soil

Indirect development

(heterogonic)

(can multiply outside host

for several generations) in soil

Direct development

Rhabditiform larvae

in soil

Filariform

larvae (450 µm)

Eosinophilia and

intermittent

epigastric pain

Autoinfection:

Transform within the intestine

into filariform larvae, which

penetrate perianal skin

or bowel mucosa,

causing:

Pruritic larva currens

Eosinophilia

Hyperinfection:

With immunosuppression, larger

numbers of filariform larvae develop,

penetrate bowel, and disseminate,

causing:

Colitis, polymicrobial sepsis,

pneumonitis, or meningitis

Larvae migrate via

bloodstream or lymphatics

to lungs, ascend airway

to trachea and pharynx,

and are swallowed.

FIGURE 232-1 Life cycle of Strongyloides stercoralis. (Reproduced with permission from RL Guerrant et al [eds]: Tropical Infectious Diseases: Principles, Pathogens and

Practice, 2nd ed, Elsevier, 2006.)

infection who are given glucocorticoids, can be fatal. Strongyloidiasis

is a frequent complication of infection with human T-cell lymphotropic

virus type 1 (HTLV-1), but disseminated strongyloidiasis is not common among patients infected with HIV-1.

Diagnosis In uncomplicated strongyloidiasis, the finding of rhabditiform larvae in feces is diagnostic. Rhabditiform larvae are ~250 μm

long, with a short buccal cavity that distinguishes them from hookworm larvae. In uncomplicated infections, few larvae are passed

and single stool examinations detect only about one-third of cases.

Serial examinations and the use of the agar plate detection method

improve the sensitivity of stool diagnosis. Again, PCR has begun to

be used more widely and provides increased diagnostic specificity. In

uncomplicated strongyloidiasis (but not in hyperinfection), microscopy-based stool examinations may be repeatedly negative. Strongyloides

larvae may also be found by sampling of the duodenojejunal contents

by aspiration or biopsy. An enzyme-linked immunosorbent assay for

serum antibodies to antigens of Strongyloides is a sensitive method for

diagnosing uncomplicated infections. Such serologic testing should be

performed for patients whose geographic histories indicate potential

exposure, especially those who exhibit eosinophilia and/or are candidates for glucocorticoid treatment of other conditions. In disseminated

strongyloidiasis, filariform larvae should be sought in stool as well as

in samples obtained from sites of potential larval migration, including

sputum, bronchoalveolar lavage fluid, or surgical drainage fluid.

TREATMENT

Strongyloidiasis

Even in the asymptomatic state, strongyloidiasis must be treated

because of the potential for subsequent dissemination and fatal

hyperinfection. Ivermectin (200 μg/kg daily for 2 days) is consistently more effective than albendazole (400 mg daily for 3 days). For

disseminated strongyloidiasis, treatment with ivermectin should

be extended for at least 14 days or at least a week after parasites

have been eradicated. In potentially immunocompromised hosts,

the course of ivermectin should be repeated 2 weeks after initial

treatment. Ivermectin has been successfully given parenterally (subcutaneously or intramuscularly) in those unable to take ivermectin

orally.

■ TRICHURIASIS

Most infections with Trichuris trichiura are asymptomatic, but heavy

infections may cause gastrointestinal symptoms. Like the other

soil-transmitted helminths, whipworm is distributed globally in the

tropics and subtropics and is most common among poor children from

resource-poor regions of the world.

Life Cycle Adult Trichuris worms reside in the colon and cecum, the

anterior portions threaded into the superficial mucosa. Thousands of

eggs laid daily by adult female worms pass with the feces and mature in

the soil. After ingestion, infective eggs hatch in the duodenum, releasing

larvae that mature before migrating to the large bowel. The entire cycle

takes ~3 months, and adult worms may live for several years.

Clinical Features Tissue reactions to Trichuris are mild. Most infected

individuals have no symptoms or eosinophilia. Heavy infections may

result in anemia, abdominal pain, anorexia, and bloody or mucoid

diarrhea resembling inflammatory bowel disease. Rectal prolapse can

result from massive infections in children, who often suffer from malnourishment and other diarrheal illnesses. Moderately heavy Trichuris

burdens also contribute to growth retardation.

1777CHAPTER 232 Intestinal Nematode Infections

Diagnosis and Treatment The characteristic 50- by 20-μm lemonshaped Trichuris eggs are readily detected on stool examination. Adult

worms, which are 3–5 cm long, are occasionally seen on proctoscopy.

PCR is being used increasingly in settings where it is available. Mebendazole (500 mg once) or albendazole (400 mg daily for 3 doses) is

safe and modestly effective for treatment, with cure rates of 30−90%.

Ivermectin (200 μg/kg daily for 3 doses) is also safe but is not quite as

efficacious as the benzimidazoles.

■ ENTEROBIASIS (PINWORM)

E. vermicularis is more common in temperate countries than in the

tropics. In the United States, ~40 million persons are infected with

pinworms, with a disproportionate number of cases among children.

Life Cycle and Epidemiology Enterobius adult worms are ~1 cm

long and dwell in the cecum. Gravid female worms migrate nocturnally into the perianal region and release up to 2000 immature eggs

each. The eggs become infective within hours and are transmitted by

hand-to-mouth passage. From ingested eggs, larvae hatch and mature

into adults. This life cycle takes ~1 month, and adult worms survive for

~2 months. Self-infection results from perianal scratching and transport of infective eggs on the hands or under the nails to the mouth.

Because of the ease of person-to-person spread, pinworm infections are

common among family members.

Clinical Features Most pinworm infections are asymptomatic.

Perianal pruritus is the cardinal symptom. The itching, which is often

worse at night as a result of the nocturnal migration of the female

worms, may lead to excoriation and bacterial superinfection. Heavy

infections have been alleged to cause abdominal pain and weight loss.

On rare occasions, pinworms invade the female genital tract, causing

vulvovaginitis and pelvic or peritoneal granulomas. Eosinophilia is

uncommon.

Diagnosis Since pinworm eggs are not released in feces, the diagnosis cannot be made by conventional fecal ova and parasite tests. Instead,

eggs are detected by the application of clear cellulose acetate tape to the

perianal region in the morning. After the tape is transferred to a slide,

microscopic examination will detect pinworm eggs, which are oval,

measure 55 × 25 μm, and are flattened along one side.

TREATMENT

Enterobiasis

Infected children and adults should be treated with mebendazole

(100 mg once) or albendazole (400 mg once), with the same treatment repeated after 2 weeks. Treatment of household members

is advocated to eliminate asymptomatic reservoirs of potential

reinfection.

■ TRICHOSTRONGYLIASIS

Trichostrongylus species, which are normally parasites of herbivorous

animals, occasionally infect humans, particularly in Asia and Africa.

Humans acquire the infection by accidentally ingesting Trichostrongylus larvae on contaminated leafy vegetables. The larvae do not migrate

in humans but mature directly into adult worms in the small bowel.

These worms ingest far less blood than hookworms; most infected

persons are asymptomatic, but heavy infections may give rise to mild

anemia and eosinophilia. In stool examinations, Trichostrongylus eggs

resemble hookworm eggs but are larger (85 × 115 μm). Treatment consists of mebendazole or albendazole (Chap. 222).

■ ANISAKIASIS

Anisakiasis is a gastrointestinal infection caused by the accidental

ingestion in uncooked saltwater fish of nematode larvae belonging to the

family Anisakidae. The incidence of anisakiasis in the United States has

increased as a result of the growing popularity of raw fish dishes. Most

cases occur in Japan, the Netherlands, and Chile, where raw fish—

sashimi, pickled green herring, and ceviche, respectively—are national

culinary staples. Anisakid nematodes parasitize large sea mammals

such as whales, dolphins, and seals. As part of a complex parasitic life

cycle involving marine food chains, infectious larvae migrate to the

musculature of a variety of fish. Both Anisakis simplex and Pseudoterranova decipiens have been implicated in human anisakiasis, but an identical gastric syndrome may be caused by the red larvae of eustrongylid

parasites of fish-eating birds.

When humans consume infected raw fish, live larvae may be

coughed up within 48 h. Alternatively, larvae may immediately

penetrate the mucosa of the stomach. Within hours, violent upper

abdominal pain accompanied by nausea and occasionally vomiting

ensues, mimicking an acute abdomen. The diagnosis can be established by direct visualization on upper endoscopy, outlining of the

worm by contrast radiographic studies, or histopathologic examination of extracted tissue. Extraction of the burrowing larvae during

endoscopy is curative. In addition, larvae may pass to the small bowel,

where they penetrate the mucosa and provoke a vigorous eosinophilic

granulomatous response. Symptoms may appear 1–2 weeks after the

infective meal, with intermittent abdominal pain, diarrhea, nausea,

and fever resembling the manifestations of Crohn’s disease. Ingestion

of Anisakis-derived proteins through consumption of fish meat containing Anisakis parasites can elicit allergic gastrointestinal and even

anaphylactic responses.

The diagnosis may be suggested by barium or other radiographic

upper gastrointestinal studies and confirmed by curative surgical resection of a granuloma in which the worm is embedded. Anisakid eggs

are not found in the stool, since the larvae do not mature in humans.

Serologic tests have been developed but are not widely available.

Anisakid larvae in saltwater fish are killed by cooking to 60°C, freezing at –20°C for 3 days, or commercial blast freezing, but usually not by

salting, marinating, or cold smoking. No medical treatment is available;

surgical or endoscopic removal should be undertaken.

■ CAPILLARIASIS

Intestinal capillariasis is caused by ingestion of raw fish infected with

Capillaria philippinensis. Subsequent autoinfection can lead to a severe

wasting syndrome. The disease occurs in the Philippines and Thailand

and, on occasion, elsewhere in Asia. The natural cycle of C. philippinensis involves fish from fresh and brackish water. When humans eat

infected raw fish, the larvae mature in the intestine into adult worms,

which produce invasive larvae that cause intestinal inflammation

and villus loss. Capillariasis has an insidious onset with nonspecific

abdominal pain and watery diarrhea. If untreated, progressive autoinfection can lead to protein-losing enteropathy, severe malabsorption,

and ultimately death from cachexia, cardiac failure, or superinfection.

The diagnosis is established by identification of the characteristic

peanut-shaped (20- × 40-μm) eggs on stool examination. Severely ill

patients require hospitalization and supportive therapy in addition

to prolonged anthelmintic treatment with albendazole (200 mg twice

daily for 10 days; Chap. 222).

■ ABDOMINAL ANGIOSTRONGYLIASIS

Abdominal angiostrongyliasis is found in Latin America and Africa.

The zoonotic parasite Angiostrongylus costaricensis causes eosinophilic

ileocolitis after the ingestion of contaminated vegetation. A. costaricensis normally parasitizes the cotton rat and other rodents, with slugs and

snails serving as intermediate hosts. Humans become infected by accidentally ingesting infective larvae in mollusk slime deposited on fruits

and vegetables; children are at highest risk. The larvae penetrate the

gut wall and migrate to the mesenteric artery, where they develop into

adult worms. Eggs deposited in the gut wall provoke an intense eosinophilic granulomatous reaction, and adult worms may cause mesenteric

arteritis, thrombosis, or frank bowel infarction. Symptoms may mimic

those of appendicitis, including abdominal pain and tenderness, fever,

vomiting, and a palpable mass in the right iliac fossa. Leukocytosis and

eosinophilia are prominent. CT with contrast medium typically shows

inflamed bowel, often with concomitant obstruction, but a definitive

diagnosis is usually made surgically with partial bowel resection.

Pathologic study reveals a thickened bowel wall with eosinophilic