Parasitology: Intestinal Protozoa, Helminths, and Immunocompromised-Host Infections

Intestinal protozoa are small and must be separated from nonpathogens, inflammatory cells, epithelial cells, yeasts, and pollen. Identification depends on size measured with an ocular micrometer, motility pattern seen only on wet mount, and nuclear and cytoplasmic detail on a permanently stained preparation (trichrome or iron hematoxylin). Report two populations from one specimen only when both are distinctly identified.

Intestinal amebae

Three genera (Entamoeba, Endolimax, Iodamoeba) inhabit the human colon; only E. histolytica invades tissue.

Dientamoeba fragilis and Pentatrichomonas hominis form no cyst. E. coli’s 8-nucleus mature cyst is the single most reliable feature separating it from the 4-nucleus E. histolytica/E. dispar/E. hartmanni group. E. hartmanni is a small-bodied look-alike separated by micrometer measurement (trophozoite 12 μm or smaller, cyst 10 μm or smaller); fixative-induced shrinkage of true E. histolytica/E. dispar can cause overcalling of E. hartmanni. Five trophozoites measuring 8, 9, 10, 11, and 9.5 μm (mean 9.5 μm) fall within the E. hartmanni range and below the usual 15-20 μm commensal E. histolytica/E. dispar range.

E. histolytica and E. dispar are morphologically identical. Only antigen or molecular testing separates them. A laboratory without such testing must report “E. histolytica/E. dispar”. Erythrophagocytosis supports E. histolytica but is not reliable enough to separate the species.

Clinical disease from E. histolytica ranges from asymptomatic carriage through amebic dysentery to amebic colitis, the more common U.S. presentation. Trophozoites that breach the mucosa can form an amebic liver abscess (ALA). Stool examination recovers organisms in fewer than half of ALA cases. Serology is positive in about 95% of ALA, 70% of active intestinal disease, and 10% of asymptomatic carriers.

Blastocystis is frequently found in asymptomatic stool; most laboratories report it only to genus. Stool forms are pleomorphic (5-40 μm), classically with a large central body; on trichrome the central body typically stains green against pink peripheral cytoplasm.

Flagellates and ciliates

Giardia duodenalis is the most widespread waterborne protozoan pathogen; chlorination alone does not reliably inactivate cysts. Trophozoites attach to duodenal mucosa. Disease ranges from asymptomatic to a malabsorptive, steatorrheic syndrome. Suspect giardiasis in diarrhea persisting beyond 10 days. Shedding is intermittent, so multiple specimens plus antigen/NAAT improve yield over a single O&P.

Trichomonas vaginalis is a common sexually transmitted infection. Direct wet mount of vaginal, prostatic, or fresh urine sediment is fast but insensitive. CDC 2021 reports wet-mount sensitivity of 44-68% versus culture, falling to about 20% within 1 hour if the slide is not examined immediately, and recommends a more sensitive molecular test, including NAAT, with a negative wet mount when possible. Most platforms are cleared for female specimens only.¹

Chilomastix mesnili, Pentatrichomonas hominis, Enteromonas hominis, and Retortamonas intestinalis are nonpathogenic commensals whose main clinical relevance is being mistaken for pathogens. Dientamoeba fragilis has flagellate ultrastructure but an ameboid light-microscopic appearance; permanent staining improves detection.

Balantioides coli (formerly Balantidium coli) is the only ciliate, and the largest protozoan, to infect humans, usually via hog, rodent, or nonhuman-primate contact. Trophozoites are 40 to >200 μm (usually 50-100 μm), uniformly ciliated, with a prominent macronucleus. Cysts are 50-70 μm with a kidney-bean-shaped macronucleus.

Cryptosporidium and the coccidia

Cryptosporidium infects the intestinal brush border and resists chlorination. Diagnosis uses acid-fast stain of concentrated sediment, immunofluorescence, or antigen/NAAT. Immunocompetent disease is self-limited (about 9-23 days after an 8-day incubation); AIDS patients can develop prolonged secretory diarrhea. Cyclospora cayetanensis infects only humans; unstained ghost oocysts are common and must be size-differentiated from Cryptosporidium. Cystoisospora belli can persist for months to years in AIDS. Intestinal Sarcocystis follows eating raw or undercooked beef or pork; wet-mount and autofluorescence are the practical detection methods.

Intestinal helminths

Adult helminth length spans 1 mm to more than 10 m, and egg size spans roughly 25-150 μm. Both dimensions are diagnostic. Transmission is direct person-to-person (Enterobius vermicularis, Hymenolepis nana); environmental maturation of an egg or larva (Trichuris, Ascaris, Trichostrongylus); ingestion of an intermediate host; or skin penetration by larvae (hookworms, Strongyloides, Schistosoma).

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Enterobiasis is the most common childhood helminthic infection in the United States, Canada, and Europe; nocturnal pruritus ani is classic. Trichuriasis produces symptoms roughly in proportion to worm burden; more than 300 worms can cause dysentery-like disease and, in children, rectal prolapse. Ascaris females produce about 200,000 eggs/day. Eggs need 4-6 weeks’ environmental maturation, then hatch after ingestion, penetrate the gut, migrate to the lungs, and cause Loeffler syndrome in previously sensitized individuals. Direct fecal smears (2 mg feces each) yielding 132, 145, and 128 Ascaris eggs average 135 eggs per slide; more than 100 eggs per 2-mg slide denotes heavy infection.

Hookworm disease reflects chronic blood loss at the site of mucosal attachment. For a burden estimated at 40 adult A. duodenale and 25 adult N. americanus, midpoint daily blood loss of 0.20 mL and 0.03 mL per worm gives (40 × 0.20) + (25 × 0.03) = 8.75 mL/day, enough to produce iron-deficiency anemia over weeks to months.

Strongyloidiasis is distinctive for autoinfection: rhabditiform larvae can mature to infective filariform larvae without leaving the host, sustaining decades-long infection. T-cell-immunocompromised hosts can develop a life-threatening hyperinfection syndrome. Larva currens is a cutaneous marker of autoinfection. Agar-plate culture or coproculture gives the best sensitivity; serology is useful when infection is suspected but not demonstrable directly.

Cestodes

T. saginata eggs are not infectious to humans, so T. saginata taeniasis cannot cause cysticercosis. Accidental ingestion of T. solium eggs causes human cysticercosis, making careful, gloved proglottid handling essential. Hymenolepis nana is the most common cestode recovered in the United States; humans can be both definitive and intermediate host via internal autoinfection. Dibothriocephalus latus can reach 10 m; a small subset of northern-European patients develop vitamin B12 deficiency because the worm competitively absorbs B12. Dipylidium caninum is a dog/cat tapeworm accidentally acquired by children who ingest an infected flea; motile proglottids likened to rice grains or cucumber seeds are usually the presenting finding.

Trematodes

Eggs are operculate except schistosome eggs, which lack an operculum and contain a mature miracidium when passed. Each species requires a specific freshwater snail as first intermediate host.

Liver flukes reside in the biliary tree. Chronic Clonorchis/Opisthorchis infection is linked to cholangiocarcinoma. Spurious Fasciola egg passage from eating infected liver is ruled out with a liver-free-diet follow-up stool exam. Lung flukes encyst in a host fibrotic capsule communicating with a bronchus, so eggs reach sputum or, if swallowed, stool. Blood flukes are dioecious. Three symptom phases are cercarial dermatitis, Katayama fever, and chronic fibrosis (hepatic pipe-stem fibrosis for intestinal species; bladder fibrosis and squamous-cell bladder carcinoma association for S. haematobium). Flotation under-recovers heavy schistosome eggs; sedimentation is required.

Tissue helminths

Wuchereria bancrofti causes classic lymphatic filariasis progressing to lymphedema and, in severe disease, elephantiasis. Loa loa produces migratory Calabar swellings and may be seen crossing the conjunctiva. Onchocerca volvulus is a leading cause of blindness in remaining endemic areas; diagnosis is by skin snip placed in saline. Zoonotic Dirofilaria produces a pulmonary coin lesion or subcutaneous nodule and rarely, if ever, circulating microfilariae in the accidental human host.

Other tissue nematodes include Dracunculus medinensis (Guinea worm); Angiostrongylus cantonensis (eosinophilic meningoencephalitis after ingesting infective larvae from snails, slugs, or contaminated produce); Trichinella (undercooked wild boar, bear, walrus, or unregulated pork; diagnosis rests on epidemiologic history plus EIA; muscle biopsy has low sensitivity); cutaneous larva migrans from dog/cat hookworm; visceral larva migrans from Toxocara canis (serology, because the organism is rarely recovered); and Anisakis/Pseudoterranova (raw-fish anisakiasis, usually diagnosed by endoscopic recovery).

Calcareous corpuscles mark cestode tissue in histologic sections. Neurocysticercosis is a leading cause of adult-onset seizures in endemic areas; enzyme-linked immunotransfer blot serology is more sensitive than crude-antigen ELISA. Hydatid disease serology uses EIA or IHA screening followed by confirmatory immunoblot.

Parasitic infection in the immunocompromised host

Cellular (T-cell) immune defects cause most parasitic predisposition. Two important exceptions are more severe giardiasis with humoral immunodeficiency and more severe babesiosis after splenectomy. HIV co-infection does not markedly worsen malaria, schistosomiasis, ascariasis, amebiasis, or filariasis. Cryptosporidiosis and toxoplasmosis are more severe or more frequent in immunocompromised hosts; reactivation CNS toxoplasmosis is classically associated with AIDS. Strongyloidiasis is a particular problem in transplant recipients, HTLV-1 infection, and chemotherapy rather than in AIDS per se.