Nematode Infections

Nematode infections in humans include ascariasis, trichuriasis, hookworm, enterobiasis, strongyloidiasis, filariasis, trichinosis, dirofilariasis, and angiostrongyliasis (rat lungworm disease), among others. The phylum Nematoda, also known as the roundworms, is the second largest phylum in the animal kingdom, encompassing up to 500,000 species. Members of Nematoda are elongated, with bilaterally symmetric bodies that contain an intestinal system and a large body cavity.

Many roundworm species are free living in nature. Recent data have demonstrated that approximately 60 species of roundworms parasitize humans. Intestinal roundworm infections constitute the largest group of helminthic diseases in humans. According to a 2005 report by the World Health Organization (WHO), approximately 0.807-1.221 billion humans have ascariasis, 604-795 million have trichuriasis, and 576-740 million have hookworm infections worldwide.[1]

The life cycle of parasitic nematodes is clinically important. Some nematode infections can be transmitted directly from infected to uninfected people; in others, the nematode eggs must undergo a process of maturation outside the host. In a third category, the parasites may spend a part of their life cycle in the soil before becoming infective to humans.

As with other parasitic infections, definitive diagnosis of nematode infections depends on demonstration of the stage of the life cycle in the host. Nematodes, as with most other worms infectious to humans, almost never complete their entire life cycle in the human host.

The life cycles of nematodes are complex and highly varied. Some species, including Enterobius vermicularis, can be transmitted directly from person to person, while others, such as Ascaris lumbricoides, Necator americanus, and Ancylostoma duodenale, require a soil phase for development. Because most helminthic 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 infection, generally develops only with prolonged residence in an endemic region.

Unlike with protozoan infections, a casual or a low degree of exposure to infective stages of parasitic nematodes usually does not result in patent infection or pathologic findings. Repeated or intense exposure to a multitude of infective stage larvae is required for infection to be established and disease to arise. Anisakis species cause erosive and/or hemorrhagic lesions in or near the main lesion, forming a tunnel through the gastric mucosa to the submucosa.

Eosinophilia and elevated serum immunoglobulin E (IgE) levels are features of many nematode infections; when unexplained, these symptoms should always prompt a search for occult roundworm infection. Humans do not appear to develop significant protective immunity to intestinal nematodes, although the mechanisms of parasite immune evasion and host immune responses to these infections have not been elucidated in detail.

Frequency

United States

Trichuriasis: Recent estimates indicate that 2.2 million people in the United States are infected with Trichuris trichiura (whipworm), mainly in the rural Southeast.

Enterobiasis: This is the most common of all helminthic infections, with an estimated 42 million cases.

Ascariasis: An estimated 4 million people, mainly in the Southeast, are infected with Ascaris species.

Hookworm: This infection still has a low degree of prevalence in the Southeast.

Strongyloidiasis: A prevalence rate of 0.4-4% has been estimated in southern states.

Trichinosis: The prevalence rate is 4-20%.

Anisakiasis: Annually, fewer than 10 cases occur in the United States.

Dirofilariasis: A total of 116 cases have been reported, originating primarily in the southeast regions in the United States.[2]

Angiostrongyliasis (rat lungworm disease): This is a rare infection that has been reported in Hawaii and Louisiana.[3]

International

According to a WHO analysis, intestinal nematode infections are most prevalent in Asia, with roughly 67% of cases.[4]

Trichuriasis: Infection with T trichiura is one of the most prevalent nematode infections worldwide; approximately 800 million persons have trichuriasis worldwide, most abundantly in warm moist regions. Infection rates of up to 75% were found in young schoolchildren in Puerto Rico.

Enterobiasis: Pinworm is also highly prevalent throughout the world, particularly in countries of the temperate zone. Children are most commonly infected. Estimated prevalence rates among children in various world regions are 4–28%.

Ascariasis: Ascaris, or roundworm, infection is the common helminthic infection in humans, with an estimated worldwide prevalence of 1 billion. The causative organism, A lumbricoides, is cosmopolitan in distribution, being most abundant in tropical countries.

Hookworm: Human infection with the 2 species of hookworm, A duodenale and N americanus, is estimated to affect approximately 550-750 million people.[5]

Strongyloidiasis: The infection is more common in tropical countries with poor sanitation, especially in countries of Southeast Asia and parts of Africa. Strongyloides stercoralis is also endemic in Jamaica and presumably elsewhere in the Caribbean. An estimated 30-100 million persons worldwide have strongyloidiasis. The prevalence of S stercoralis infection among individuals with HIV infection is 5.1%.[6]

Trichinosis: Trichinella species are distributed throughout the world and are spread widely in nature among a large number of carnivorous animals, with humans acting as an incidental host. Trichinosis has been a major public health problem and has been reported in many Asian countries, including China, Japan, Korea, and Thailand.

Dracunculiasis: Estimates of the number of people infected with Dracunculus medinensis in Africa, the Middle East, India, and other tropical areas range from 50-150 million. An aggressive eradication campaign has been underway to eliminate D medinensis, which is called the Guinea worm.

Filariasis: An estimated 120 million people are infected with Wuchereria bancrofti, Brugia malayi, and Brugia timori.

Loiasis: Loa loa is irregularly distributed in Africa. It is estimated that between 3 and 13 million people in West and Central Africa are infected.

Onchocerciasis: Onchocerca volvulus infects 20 million people in West, Central, and East Africa and another 1 million people in scattered foci in Central America and South America. The disease caused by this filarial worm is called river blindness.

Anisakiasis: Approximately 20,000 cases of anisakiasis are reported annually worldwide; over 90% are from Japan and most others from Spain, the Netherlands, and Germany, depending on the habits of fish consumption.[7]

Dirofilariasis: The highest incidence of human cases has been recorded in Mediterranean countries (Italy, southern France, Greece). Dirofilariasis has been reported in some eastern European countries, namely Ukraine, Russian Federation, and Belarus, in the last two decades. Italy has the most number of cases of human dirofilariasis.[8]

Angiostrongyliasis (rat lungworm disease): This is an uncommon infection that mostly affects the Pacific Basin and Southeast Asia. Isolated cases have been reported in the Caribbean, Africa, and Australia.[3]

Mortality/Morbidity

Nematode infections are usually asymptomatic or subclinical.

Strongyloidosis may be fatal in immunocompromised patients and in newborns.

Intestinal nematodes can cause some GI problems (eg, abdominal pain, diarrhea, anorexia, weight loss, malaise).

Hookworms can cause serious anemia.

Onchocerciasis can result in blindness (river blindness).

Trichinosis can cause life-threatening manifestations, including myocarditis, CNS involvement, and pneumonitis.

Larvae of Anisakis species may become embedded in the gastric mucosa; endoscopy may reveal erythema, edema, severe erosive gastritis, a tumorlike nodule, or ulcerations. Anisakiasis has been reported to be associated with allergy reactions in some individuals.[9]

Patients with ocular dirofilariasis often report discomfort, ocular pain, grittiness, and eye redness.[10]

Angiostrongyliasis (rat lungworm disease) has a presentation similar to that of bacterial meningitis. Rarely, neurologic dysfunction or death can occur.[3]

Some of the more serious nematode infections result in symptoms from inflammatory responses in vital organs and nutritional deficiencies.

Race

Nematode infections have no known racial predilection.

Sex

Nematode infections have no known sexual predilection.

Age

E vermicularis infection (pinworm) is more common in children than in adults.

Light-to-moderate nematode infections carry a good prognosis. Prognosis depends on the organ infected and the extent of the infection.

Ascariasis should always be treated because of the risk of migrating adult worms.

Long-term diethylcarbamazine treatment and immunomonitoring of patients with filariae are essential in endemic areas to arrest and prevent pathology.

Angiostrongyliasis (rat lungworm disease) typically resolves without treatment.[3]

Avoid fecally contaminated food, water, and soil.

Avoid bites by arthropod vectors. Use insect repellants and other protective measures, eg, proper clothing.

Avoid rivers, streams, and soils known to be infected.

Several clinical signs and symptoms can occur in patients with nematode infections.

• Lung invasion - Löeffler or Löefflerlike syndrome (ascariasis, hookworm infections, strongyloidiasis)

  • Fever

  • Cough

  • Blood-tinged sputum

  • Wheezing

  • Rales

  • Dyspnea

  • Substernal pain

  • Pulmonary consolidations

  • Eosinophilia

  • Urticaria

  • Asthma

  • Angioneurotic edema

• Intestinal invasion

  • May be asymptomatic (small number)

  • Abdominal pain (usually vague)

  • Abdominal cramps/colic

  • Diarrhea

  • Vomiting (rarely)

  • Constipation (occasionally)

• Muscle and other tissue invasion - Trichinosis

  • Myalgias

  • Fever

  • Edema and spasm

  • Periorbital and facial edema

  • Photophobia

  • Sweating

  • Conjunctivitis

  • Weakness or prostration

  • Pain upon swallowing

  • Subconjunctival, retinal, and ungual hemorrhages

  • Rashes and formication

  • Encephalitis, myocarditis, nephritis

  • Pneumonia, meningitis, neuropathy

• Lymphatic filariasis - W bancrofti, B malayi, B timori

  • Inflammatory signs (pain, tenderness, swelling, erythema)

  • Lymphadenitis/lymphangitis

  • Orchitis

  • Fever

  • Abscesses

  • Obstructive signs (lymphatic varices, hydrocele)

  • Lymphedema and elephantiasis

  • Chyluria

  • Hypereosinophilia

• Loiasis - Loa loa

  • Calabar swellings (recurrent subcutaneous inflammation/swelling)

  • Eye worm (adults or larvae migrating under conjunctiva)

  • Eosinophilia (may exceed 70%)

  • Fever, irritability, urticaria, and pruritus

• Onchocerciasis - O volvulus

  • Dermatitis

  • Nodules

  • Lymphadenitis

  • Ocular changes

    • Intraocular microfilariae

    • Punctate keratitis

    • Sclerosing keratitis

    • Anterior uveitis chorioretinitis

    • Optic neuritis

    • Optic atrophy

    • Glaucoma

    • Blindness (river blindness)

• Dracunculiasis - D medinensis, Guinea worm disease

  • Allergic manifestations

    • Erythema

    • Urticaria

    • Pruritus

    • Nausea

    • Vomiting

    • Giddiness

    • Syncope

    • Fever (occasionally)

  • Local lesions

    • Papule

    • Sterile blister

    • Ulceration

    • Abscesses

  • Worm protrusion from skin

• Toxocariasis - Toxocara canis/Toxocara cati, visceral or ocular larva migrans

  • Eosinophilia

  • Visceral larva migrans

  • Ocular larva migrans

• Cutaneous larva migrans - Ancylostoma braziliense,Ancylostoma caninum, creeping eruption

  • Itching and red papules

  • Serpiginous track

  • Edema and acute inflammation

  • Scars

  • Secondary infection

• Anisakiasis -Anisakis simplex,Pseudoterranova decipiens

  • Violent epigastric pain

  • Mild fever

  • Nausea

  • Vomiting

  • Diarrhea

  • Allergic reactions

• Dirofilariasis

  • Chest pain, cough, hemoptysis, fever, and malaise in the pulmonary type

  • Creeping eruption and elevated sinuous track under the skin in the subcutaneous type

  • Ocular pain, grittiness, and eye redness in the ocular type

• Angiostrongyliasis (rat lungworm disease)[3]

  • Nausea/vomiting

  • Neck stiffness

  • Headaches (may be global and severe)

  • Abnormal sensations in the legs and arms (some cases)

  • May report consumption of raw or undercooked slugs or snails

T trichiurainfections

In heavily infected people, trichuriasis appears to manifest as mild anemia, eosinophilia, bloody diarrhea (classic trichuris dysentery syndrome), growth retardation (chronic trichuris colitis with growth retardation), abdominal pain, finger clubbing, and rectal prolapse (especially in children). See the image below.

E vermicularisinfection (pinworm)

The most common symptom of pinworm infection is nocturnal perianal pruritus. Occasionally, the migration of the parasite produces ectopic disease (eg, appendicitis, vulvovaginitis, chronic salpingitis, ulcerative lesions in the small or large bowel).[11] Enuresis has been blamed on the pinworm.

A lumbricoidesinfection

A more serious complication of ascariasis is encountered when a mass of worms obstructs the lumen of the small bowel. This acute abdominal condition is commonly observed in children with heavy infections. The presentation is similar to that of acute intestinal obstruction, with vomiting, abdominal distention, and cramps.

Another obstructive syndrome is encountered when Ascaris worms invade the biliary duct and cause pancreatic-biliary ascariasis. The most common presenting feature is abdominal pain, observed in 98% of patients. Less common features include ascending cholangitis, acute pancreatitis, and, rarely, obstructive jaundice.

Ascariasis in pregnant women results in intrauterine growth retardation. See the image below.

Hookworms

The major manifestations of hookworm disease include iron deficiency anemia and chronic protein energy malnutrition. The development of these clinical features depends not only on the worm burden but also on the amount of absorbable dietary iron.

During the phase of worm attachment to small intestine mucosa, abdominal pain, diarrhea, and weight loss may be noted. In addition, malabsorption has been reported in children and, less commonly, in adults.[12]

S stercoralisinfection

Burning or colicky abdominal pain, often epigastric, occurs and is associated with diarrhea and the passage of mucus.

Some patients with strongyloidiasis report nausea, vomiting, and weight loss, with evidence of malabsorption or of protein-losing enteropathy.

Massive larval invasion of the lungs and other tissues may occur with hyperinfection, usually in immunocompromised hosts. In this syndrome, the worm is able to complete its entire life cycle in the human, and the symptoms are related to the large burden of larvae migrating in the host.

Severe generalized abdominal pain, diffuse pulmonary infiltrates, ileus, shock, and meningitis or sepsis due to gram-negative bacilli may occur. See the image below.

T spiralisinfection

Myositis with pain, swelling, and weakness is common; it usually first develops in the extraocular muscles and then involves the masseters, neck muscles, limb flexors, and lumbar muscles. Some patients report headache, cough, shortness of breath, hoarseness, and dysphagia.

Anisakiasis

The ingestion of a parasitized fish with a nematode of the Anisakis genus may elicit symptoms within few hours.

Four principal clinical syndromes associated to anisakiasis have been described: gastric, intestinal, ectopic (or extragastrointestinal), and allergic. The onset of gastric anisakiasis begins within a few hours (generally 1 to 2 hours), when a live Anisakis larva reaches the human stomach.

Acute phase of the infection elicits severe epigastric pain, vomiting, diarrhea, and a mild fever. Generally, acute symptoms resolve within a few days, but untreated gastric disease can lead to chronic ulcerlike symptoms lasting for weeks to months.

Rare complications include small bowel obstruction, ileal stenosis, intussusception, intestinal perforation, and pneumoperitoneum.

Dirofilariasis

Dirofilaria species are nematodes that infect domestic and wild canids, transmitted by several species of mosquitoes. Dirofilaria immitis causes severe disease (heartworm disease) in dogs and other carnivores and occasionally infects humans, while Dirofilaria repens usually causes a nonpathogenic subcutaneous infection in dogs and is the principal agent of human dirofilariasis in the Old World.

Dirofilariasis causes two main clinical syndromes: pulmonary dirofilariasis (caused by D immitis) and ocular or subcutaneous dirofilariasis (caused by several different dirofilarial species, particularly D repens). In addition to these syndromes, human dirofilariasis has been reported at other sites, such as the central nervous system, male genital system, peritoneal cavity, liver, or buccal mucosa.[8]

The diagnosis of Dirofilaria infection in humans is affected by the localization of the worm and the clinical symptoms. Serological investigations are not helpful in human cases.

The nematode can be removed via surgery, a practice that is also needed for etiological diagnosis and the exclusion of other severe diseases.[13]

Angiostrongyliasis (rat lungworm disease)

Angiostrongylus cantonensis infection has a presentation similar to that of bacterial meningitis (eg, nausea/vomiting, stiff neck, headaches). The infection can last from 2-8 weeks (or longer) but usually self-resolves without treatment.[3]

The following are potential causes of nematode infections:

• Ingestion of mature eggs in fecally contaminated food or drink

• Larval penetration of skin (hookworms and S stercoralis)

• Larvae introduced into human host by arthropod vector (mosquitoes for filariasis and flies for O volvulus and Dirofilaria species)

• Ingestion of raw or undercooked fish or cephalopods contaminated by third stage larvae (anisakiasis) or raw or undercooked snails or slugs (angiostrongyliasis [rat lungworm disease])

Potential complications of nematode infections are as follows:

• Vomiting worms - Ascariasis, Anisakiasis

• Worm migration

  • Cholangitis (migration to common bile duct)

  • Pancreatitis (migration to pancreatic duct)

  • Appendicitis (migration to appendix)

  • Diverticulitis (migration to diverticula)

• Liver abscess

• Intestinal obstruction, volvulus

• Intussusception

• Bowel penetration

• Anemia, hypoproteinemia - Hookworm

• CNS infection - Strongyloides infection

• Onchocerciasis - Blindness

• Filariasis - Lymphatic destruction leading to severe edema (elephantiasis)

• Anisakiasis - Rare complications include small bowel obstructions, ileal stenosis, intussusception, intestinal perforation, and pneumoperitoneum

• Neurohelminthiasis - CNS migrations and infection

• Visceral worms

  • Hepatitis

  • Splenomegaly

  • Pleuritis

  • Peritonitis

  • Eosinophilic granuloma

  • Other organ damage because larvae migrate for as long as 6 months

Several approaches are available to identify nematodes, from the basic traditional morphological identification methods to the more complex high-throughput sequencing technologies. The morphological and morphometric features allow identification of nematodes within their respective genus. The species can be identified based on the morphological features of the sexual organs of adult male nematodes.

The morphology of the eggs or larvae collected from feces, along with any clinical symptoms, is usually sufficient to diagnose a human nematode infection.

The detection of an antibody response mounted toward a nematode infection constitutes another frequently used diagnostic strategy. Sensitive immunological methods such as enzyme-linked immunosorbent assay (ELISA) are useful to detect antibodies in the serum.[14]

Molecular methods are effective for identification of nematodes. Polymerase chain reaction (PCR)–based methods and multiplex PCR have provided solutions in problems related to differential diagnosis.[15]

Laboratory studies are as follows:

• Stool examination for intestinal nematodes using native, zinc sulfate flotation, or formalin-ethyl acetate sedimentation techniques (based on characteristics of eggs or larvae in stool or adult worm, if passed; cellophane-tape impression for pinworms)
• Examination of larvae or adult worms taken from the tissue, characteristic microfilariae on blood smear, eosinophilia
• Filariasis - Membrane filtration technique, Knott technique, and thick blood smear (Giemsa stained)
• Distinction of species by larval examination - Challenging and may require expert examination; fecal culture of at least one week necessary to identify, for example, the first-stage (L1) or the infective third-stage (L3) larvae in order to differentiate between the human hookworms ( A duodenale, N americanus) and S stercoralis nematodes ^[14]
• Onchocerciasis - Identified by skin snip/biopsy showing larvae
• Toxocariasis - Enzyme-linked immunosorbent assay (ELISA) and, occasionally, biopsy
• Trichinosis - Muscle biopsy and ELISA
• Dirofilariasis - The definitive diagnosis is obtained after worm removal using microscopic examination
• Anisakiasis - Latex-based agglutination, immunofluorescence, indirect hemagglutination, complement fixation, immunoblotting, and ELISA
• Angiostrongyliasis (rat lungworm disease) - Eosinophilia in blood (>5%) or cerebrospinal fluid (CSF) (>10%) ^[3]

Imaging studies are as follows:

• Larvae in sputum or adult worms observed on radiologic studies (uncommon)

• Lung radiography for Löeffler syndrome

• Ultrasonography - Useful in the diagnosis of ascariasis as a cause of biliary tract disease

Onchocerciasis: Skin snip, nodulectomy, slit-lamp examination, and Mazzotti test are helpful.

Characteristic eggs, worms, or larvae in tissue

Nematode infections need to be identified and treated accordingly.

In dracunculiasis, the best treatment is direct removal of worms from tissue, taking care not to break the worm.

Treat secondary infections.

Acute intestinal obstruction and perforation in patients with ascariasis may require surgical treatment.

Long-standing lymphatic filariasis due to W bancrofti and B malayi infection may require surgical intervention to increase lymphatic drainage. This is unusual and likely observed in long-term residents of endemic areas who have been subjected to extensive exposure to the parasite.

Consultations are as follows:

• Gastroenterologists

• Parasitologists

• Radiologists

• Dermatologists

• Chest diseases specialists

No special diet is required.

No restrictions are necessary. In lymphatic filariasis, if edema is a problem, the patient may want to elevate legs while sitting.

Preventive measures are as follows:

• Good hygiene and sanitation

• Avoidance of sources of infection (eg, arthropod bites, rivers/streams, contaminated soils, consumption of raw or undercooked fish, snails, and slugs)

• Public health activities such as vector control

Patients who have undergone treatment for nematode infections should undergo follow-up stool studies at 2 weeks and re-treatment, if necessary.

The goals of pharmacotherapy are to eradicate the infestation, to reduce morbidity, and to prevent complications.[16]

Class Summary

Parasite biochemical pathways are different from the human host; thus, toxicity is directed to the parasite, egg, or larvae. Mechanism of action varies within the drug class. Antiparasitic actions may include the following:

- Inhibition of microtubules, causing irreversible block of glucose uptake

- Tubulin polymerization inhibition

- Depolarizing neuromuscular blockade

- Cholinesterase inhibition

- Increased cell membrane permeability, resulting in intracellular calcium loss

- Vacuolization of the schistosome tegument

- Increased cell membrane permeability to chloride ions via chloride channels alteration

Albendazole (Albenza)

Used for hookworm, pinworm, and roundworm. Decreases ATP production in worm, causing energy depletion, immobilization, and, finally, death.

Mebendazole (Vermox)

Indicated for treating E vermicularis (pinworm), T trichiura (whipworm), A lumbricoides (common roundworm), A duodenale (common hookworm), N americanus (American hookworm) in single or mixed infections. Efficacy varies as a function of such factors as preexisting diarrhea and GI transit time, degree of infection, and helminth strains. Causes worm death by selectively and irreversibly blocking uptake of glucose and other nutrients in susceptible adult intestine where helminths dwell.

Ivermectin (Mectizan)

Member of avermectin class (broad-spectrum antiparasitic agents). Unique mode of action. Binds selectively with high affinity to glutamate-gated chloride ion channels in invertebrate nerve and muscle cells. Increases permeability of cell membrane to chloride ions. Results in hyperpolarization of nerve or muscle cell, causing parasite paralysis and death. Also affects other ligand-gated chloride channels (eg, those gated by GABA). Active against various life-cycle stages of most nematodes. Active against O volvulus tissue microfilariae but not adult form. Activity against S stercoralis limited to intestinal stages.

Piperazine (Vermizine)

Readily absorbed from GI tract, partially degraded in vivo, and excreted in urine. Paralyzes worm muscle; thus, worm expelled by normal intestinal peristalsis. Exhibits wide therapeutic index. Not available in the United States.

Pyrantel pamoate (Antiminth, Pin-Rid)

Depolarizing neuromuscular blocking agent and cholinesterase inhibitor that results in spastic paralysis of worm. Active against E vermicularis (pinworm), A lumbricoides (roundworm), and A duodenale (hookworm).

Diethylcarbamazine citrate (Hetrazan)

Effective in treating filariasis specific for W bancrofti, B malayi, and L loa. Does not contain any toxic metallic elements. Not recommended as DOC because of severe adverse effects. Recommended if therapy with mebendazole fails or unavailable.