Nematodes: Intestinal & Tissue Roundworms

Routes of infection

How roundworms get in. The route of entry is the first clue to the species. Swallowed eggs transmit Enterobius, Ascaris, Trichuris, and Toxocara. Larvae encysted in undercooked meat transmit Trichinella. Larvae living in soil penetrate bare skin to cause Strongyloides and hookworm infection. Insect bites deliver the filarial worms: Onchocerca by black flies, Loa loa by deer flies, and Wuchereria and Brugia by mosquitoes.

Eosinophilia. Worms that migrate through tissue (Ascaris and hookworm larvae in the lungs, Strongyloides, Trichinella, Toxocara, filariae) drive eosinophilia; pinworms stay in the bowel lumen and usually do not.

Intestinal nematodes

Enterobius vermicularis (pinworm). The most common helminth infection in the United States, especially in young children. Eggs on fingers, bedding, and toys are swallowed, and gravid females crawl out at night to lay eggs on the perianal skin, causing nocturnal perianal itching; scratching carries eggs back to the mouth. It can also cause vulvovaginitis in girls. A morning adhesive tape test picks up the eggs, which are rarely found in stool. Pyrantel pamoate or albendazole is given, repeated in 2 weeks, and the whole household is treated.

Ascaris lumbricoides. After swallowed eggs hatch, larvae cross the bowel wall, travel through the portal blood and liver to the lungs, break into alveoli, and are coughed up and swallowed. The lung passage causes Löffler syndrome: cough, wheeze, migratory infiltrates, and eosinophilia. Adults, the largest intestinal roundworms, live in the small intestine; heavy loads can obstruct the ileum in children or migrate into the bile ducts, causing cholangitis or pancreatitis. Stool shows knobby, thick-shelled eggs.

Hookworms. Necator americanus and Ancylostoma duodenale larvae penetrate bare feet (an itchy "ground itch"), pass through the lungs, and attach to the small-bowel mucosa, where adults feed on blood. Chronic blood loss causes microcytic iron-deficiency anemia and hypoalbuminemia and stunts children's growth.

Cutaneous larva migrans. Dog and cat hookworm larvae (Ancylostoma braziliense, A. caninum) in beach sand or soil enter human skin but cannot go deeper. They leave an intensely itchy, raised, serpiginous track that creeps 1–2 cm per day on the feet or buttocks. The eruption is self-limited, but ivermectin or albendazole speeds cure.

Trichuris trichiura (whipworm). Swallowed eggs grow into adults that thread their thin ends into the colonic mucosa. Heavy infection in children causes bloody diarrhea, anemia, growth delay, and rectal prolapse. Stool shows barrel-shaped eggs with bipolar plugs.

Strongyloides stercoralis

Life cycle. Filariform larvae penetrate skin, pass through the lungs, and are swallowed to the duodenum, where females lay eggs that hatch inside the bowel, so stool shows rhabditiform larvae rather than eggs. Some larvae mature in the gut and reinvade through the bowel wall or perianal skin. This autoinfection lets infection persist for decades after the patient has left an endemic area, with chronic eosinophilia and larva currens, an urticarial track on the buttocks and thighs that moves several centimeters per hour.

Hyperinfection. Corticosteroids, transplant immunosuppression, and HTLV-1 coinfection blunt the Th2 response that holds the worm in check. Autoinfection then accelerates, and huge numbers of larvae invade the lungs and other organs, carrying enteric bacteria with them: gram-negative sepsis or meningitis (E. coli, Klebsiella) follows, with high mortality. Steroids may suppress eosinophilia, so its absence does not exclude the diagnosis. Ivermectin is the treatment, and people from endemic regions are screened by serology, or treated empirically, before immunosuppression.

Before starting high-dose steroids or transplant immunosuppression in a patient from an endemic area, think of Strongyloides: unrecognized hyperinfection is often fatal.

Tissue nematodes: Trichinella and Toxocara

Trichinella spiralis. Larvae encysted in undercooked pork or wild game (bear, walrus) are released in the stomach and mature in the small intestine, causing brief GI upset. Their offspring travel through the blood and encyst in striated muscle, producing fever, periorbital edema, myalgia and weakness, elevated CK, marked eosinophilia, and splinter hemorrhages. Serology or muscle biopsy confirms it; treatment is albendazole, with corticosteroids for severe disease.

Toxocara canis and T. cati. Toddlers with pica swallow eggs from soil or sandboxes contaminated by dog or cat feces. Humans are dead-end hosts, so larvae wander through tissues without maturing. Visceral larva migrans brings fever, hepatomegaly, wheezing, and marked eosinophilia. Ocular larva migrans, usually in older children, forms a retinal granuloma with leukocoria that can mimic retinoblastoma. Albendazole is used, with steroids for eye disease; deworming puppies and covering sandboxes prevent infection.

Filarial nematodes

Onchocerca volvulus. Black flies (Simulium) breed along fast rivers in Africa. Adult worms sit in subcutaneous nodules, while microfilariae migrate through the skin and eyes, causing intensely pruritic dermatitis with depigmentation ("leopard skin") and keratitis or chorioretinitis that ends in river blindness. Skin snips show microfilariae. Ivermectin, sometimes with doxycycline, is the treatment; DEC is avoided because rapid microfilarial death triggers a severe inflammatory (Mazzotti) reaction that can damage the eyes.

Loa loa. Deer flies (Chrysops) in West and Central African rainforest transmit this "eye worm." Adults migrate through subcutaneous tissue, causing transient, itchy Calabar swellings of the limbs, and may be seen crossing the conjunctiva. Microfilariae circulate in daytime blood. DEC is curative, but DEC or ivermectin can provoke fatal encephalopathy when microfilarial counts are very high, so the load is measured first.

Wuchereria bancrofti and Brugia malayi. Mosquitoes transmit these lymphatic filariae. Adults in lymphatic vessels cause recurrent lymphangitis and, over years, lymphedema, elephantiasis of the legs or scrotum, and hydrocele. Microfilariae circulate at night, so blood is drawn near midnight. Tropical pulmonary eosinophilia (nocturnal cough, wheeze, very high eosinophil counts and IgE) is a hyperimmune form. Treatment is DEC plus albendazole; doxycycline kills the Wolbachia bacterial endosymbiont on which adult worms depend.

Anthelmintic pharmacology

• Benzimidazoles (albendazole, mebendazole) — bind worm β-tubulin and block microtubule polymerization, so glucose uptake fails; broad activity against intestinal nematodes, and albendazole also treats Trichinella and Toxocara.
• Ivermectin — opens glutamate-gated chloride channels in worm nerve and muscle, hyperpolarizing them and causing flaccid paralysis; the drug of choice for Strongyloides and Onchocerca and an option for cutaneous larva migrans.
• Pyrantel pamoate — a depolarizing nicotinic agonist that causes spastic paralysis, so the worms are expelled; used for pinworm and other intestinal worms.
• Diethylcarbamazine (DEC) — kills microfilariae of Wuchereria, Brugia, and Loa loa; contraindicated in onchocerciasis.