Nematode Infections

Epidemiology

A. lumbricoides is the most prevalent nematode infection worldwide, affecting approximately 730 million people in sub-Saharan Africa, South and Southeast Asia, and Latin America, primarily in rural areas of high population density that lack adequate sanitation or treatment of sewage or where untreated human feces are used as fertilizer. Climate is an important determinant of disease since warm temperatures and adequate moisture are needed for embryonation of eggs in soil. In endemic areas, the prevalence and intensity of infection increase significantly during the first 2 to 3 years of life, remain high between the ages of 4 and 15 years, and then decline during adulthood.

Pathobiology

In the stomach, the egg’s outer shell is dissolved by gastric acid, thereby releasing larvae into the small intestine, where they penetrate the intestinal wall and enter the portal circulation. The larvae migrate to the pulmonary vasculature, where they penetrate the alveoli, ascend the bronchial tree, and are swallowed back into the intestinal tract, where they develop into adult worms 9 to 11 weeks after egg ingestion. Each day, a female adult Ascaris worm releases over 200,000 eggs that are expelled in feces. Fertilized eggs ( Fig. 327-2 ) become infectious after embryonating in warm, moist, shady soil. Eggs are resistant to extreme temperatures and to desiccation, and they can survive up to 15 years in the environment.

Clinical manifestations are associated with heavy worm burdens and result from larval migration through the lungs and from parasitism of the gastrointestinal tract by adult worms. During the pulmonary phase of the life cycle, A. lumbricoides larvae can induce an intense reaction that is due to both physical disruption and a hypersensitivity response to secreted antigens. This phenomenon is more common in areas in which transmission is seasonal, such as on the Arabian Peninsula, where outbreaks of pneumonitis typically follow the rainy season because of resumption of transmission.

Clinical Manifestations

Low-intensity A. lumbricoides infections are usually asymptomatic, but heavy worm burdens cause symptoms including sudden onset of wheezing, dyspnea, paroxysmal nonproductive cough, and high fever. Symptoms may persist for 2 to 3 weeks before resolving spontaneously. Respiratory symptoms may coincide with or be preceded by urticarial rash, angioedema, abdominal pain, and vomiting.

With moderate or heavy infections, a mass of worms can cause obstruction in the small intestine or migration of worms to the biliary tree, pancreatic duct, or appendix. Intestinal obstruction, which is more common in young children because of their smaller lumen size, is characterized by colicky abdominal pain and vomiting that may progress to signs of intestinal perforation and be confused with acute appendicitis ( Chapter 128 ). Hepatobiliary and pancreatic ascariasis are more common in adults. Chronic intestinal infection can manifest as abdominal pain and distention, diarrhea, and nausea. More insidious effects, especially in children, include decreased protein and fat absorption, development of vitamin A and C deficiencies, and lactose intolerance, which together lead to asthenia, stunted growth, and impaired cognitive development.

Diagnosis

Diagnosis of ascariasis is usually made by microscopic examination of a sample of feces for characteristic thick-shelled eggs. Polymerase chain reaction (PCR) testing, although currently available only in specialized laboratories as a research tool, is also highly sensitive and specific. However, during the pulmonary phase of infection, ova will not be detectable in feces because adult worms have not yet matured and begun producing eggs; instead, larvae, as well as eosinophils or Charcot-Leyden crystals (formed from the breakdown of eosinophils), may be visualized on microscopic examination of sputum. Pulmonary disease is also usually characterized by peripheral eosinophilia and transient infiltrates on chest radiographs. The diagnosis of intestinal or biliary obstruction caused by A. lumbricoides is usually made by ultrasound examination or endoscopic retrograde cholangiopancreatography (ERCP).

Treatment

Prevention

The definitive means of preventing Ascaris infection is improvement of hygiene and proper disposal of human waste. In endemic communities where this is not feasible, morbidity control consists of regular (usually annual) mass administration of an anthelminthic medication such as albendazole or mebendazole to preschool and school-aged children.

Prognosis

Untreated, ascariasis may lead to chronic infection that persists for years and can result in clinical complications ranging from rarely fatal intestinal or biliary obstruction to more insidious sequelae such as malnutrition. Although treatment with albendazole is highly effective, children living in endemic communities often become reinfected within months owing to continued exposure from the contaminated environment.

Epidemiology

Over 400 million people are infected with hookworms worldwide. N. americanus is widespread, whereas infection with A. duodenale is more geographically restricted. The highest prevalence of infection occurs in rural areas of tropical and less developed countries, where environmental and socioeconomic conditions favor transmission. Like A. lumbricoides , hookworm eggs require soil of adequate moisture and warm temperature to incubate and develop into larvae. Equally important determinants of infection are poverty and lack of access to adequate sanitation and clean water. The prevalence of infection increases with age in children living in endemic areas until it plateaus by about age 10 years. By comparison, the intensity of infection rises at a slower rate during childhood, reaching a plateau by about age 20 years and then increasing again in the elderly.

Although cutaneous larva migrans is found throughout the tropics, in the United States it is diagnosed primarily in travelers who have recently returned from a tropical beach vacation, especially in the Caribbean, South and Central America, and Southeast Asia. Occasionally, autochthonous cases (originating where found) have been reported in the United States, usually from southeastern coastal states such as Florida and Texas. Cutaneous larva migrans occurs when larvae of the dog or cat hookworms ( A. caninum or A. braziliense , respectively) are expelled in their feces, contaminate moist soil or sand, and then come into contact with exposed skin. Other animal hookworms such as U. stenocephala and B. phlebotomum are less common causes.

Pathobiology

Infection occurs when exposed skin comes in contact with infective filariform larvae in fecally contaminated soil or grass. Larvae penetrate the skin and enter the venous circulation. After reaching the pulmonary vasculature, larvae penetrate into alveolae, ascend the bronchial tree to the larynx, and are swallowed into the gastrointestinal tract. Larvae develop into sexually mature adult worms 5 to 9 weeks after skin penetration. Adult hookworms reside in the lumen of the small intestine, where they attach to the mucosa by means of cutting teeth ( A. duodenale ) or a rounded cutting plate ( N. americanus ). After mating, female worms produce eggs that are expelled from the body in feces; A. duodenale female worms lay approximately 28,000 eggs daily, whereas the output from N. americanus worms averages around 10,000 a day. Hookworm eggs hatch in warm, moist, sandy soil and release larvae that can infect another host. Humans are the only natural definitive hosts for these two parasites, and there are no intermediate or reservoir hosts. A. duodenale worms survive on average for 1 year in the human intestine, whereas N. americanus lives for 3 to 5 years.

The major pathology of hookworm infection is the associated gastrointestinal blood loss and resulting iron deficiency anemia. Hookworms attach to the intestinal mucosa and secrete enzymes that enable them to invade submucosal tissues and ingest villous tissue and blood. Hemoglobinases within the hookworm’s digestive canal degrade host hemoglobin for use as an essential nutrient source. The amount of blood loss is directly related to the total worm burden. A. duodenale causes more blood loss than N. americanus : each N. americanus worm results in a daily blood loss of 0.03 to 0.1 mL, whereas the corresponding figure for A. duodenale is between 0.15 and 0.26 mL.

Clinical Manifestations

The clinical features of hookworm infection are related to the initial larval migration through the skin and other tissues and the acute and chronic manifestations resulting from parasitism of the gastrointestinal tract by adult worms. Repeated skin exposure to hookworm larvae can result in a hypersensitivity reaction known as “ground itch,” a pruritic erythematous and papular rash that appears most commonly on the hands and feet. In contrast, when zoonotic hookworm larvae penetrate the skin to produce cutaneous larva migrans, most commonly on the feet, legs, and buttocks, they are unable to complete their life cycle in the human host and eventually die after causing a typical rash consisting of intensely pruritic, erythematous serpiginous tracks (see Fig. 327-3 ). Tracks appear after an incubation period of a few days, can be single or multiple, and advance by millimeters to a few centimeters each day. Vesiculobullous or papular lesions may develop along the tracks, as can secondary bacterial infection because of scratching. Untreated, lesions usually heal spontaneously within weeks to months following death of the larvae in the skin.

Migration of hookworm larvae through the lungs may induce mild and transient pulmonary symptoms consisting of dry cough, sore throat, wheezing, and low-grade fever. Uncommonly, acute symptomatic disease may follow the oral ingestion of A. duodenale larvae, known as Wakana syndrome, which is characterized by pharyngeal irritation, cough, dyspnea, hoarseness, nausea, and vomiting.

Gastrointestinal symptoms and signs caused by hookworm infection are uncommon. Instead, the manifestations of hookworm disease occur when intestinal blood loss exceeds the nutritional reserves of the host and results in iron deficiency anemia. Usually only moderate- and high-intensity (≥2000 eggs per gram of feces) hookworm infections produce clinical disease, which resembles that of iron deficiency anemia secondary to other causes ( Chapter 145 ). In addition, the protein losses associated with heavy hookworm infection can result in hypoproteinemia and anasarca. Clinical manifestations of iron deficiency anemia include weakness, palpitations, fainting, dizziness, dyspnea, lassitude, and headache. Uncommonly, patients may have constipation or diarrhea with occult blood in the stool or even frank melena, especially in children; there may also be an urge to eat soil (pica). Overwhelming hookworm infection may cause listlessness, coma, and even death, especially in infants. Because children and women of reproductive age have lower iron reserves, they are at increased risk of symptomatic disease.

Diagnosis

The diagnosis of hookworm infection is made by microscopic identification of characteristic eggs in the stool. The eggs of N. americanus and A. duodenale cannot be distinguished because both are colorless and have a single thin hyaline shell with blunted ends; they range in size from 55 to 75 μm by 36 to 40 μm. Egg concentration techniques, such as the formalin–ethyl acetate sedimentation method, can be used to detect even light infections, although a direct wet mount examination is adequate for detecting moderate to heavy infections. As with A. lumbricoides , PCR testing that has been reported to be highly sensitive and specific is performed by a few specialized laboratories but is not commercially available or approved as a diagnostic test. In addition, eosinophilia is a common finding in chronic infection and during larval migration through the lungs.

Treatment

Prevention

The ideal method for preventing hookworm infection is improvement in hygiene and proper disposal of human waste. In endemic communities where these public health measures have not been accomplished, control of disease consists of regular (at least annual) mass administration of single doses of an anthelminthic medication such as albendazole or mebendazole. For cutaneous larva migrans, tourists should be advised to wear shoes or sandals when walking on beaches and to avoid areas frequented by stray cats and dogs.

Prognosis

Severe iron deficiency anemia caused by hookworm during pregnancy can result in adverse consequences for the mother, the fetus (spontaneous abortion, intrauterine growth restriction), and the neonate (anemia, failure to thrive). In children, the anemia and protein malnutrition ( Chapter 197 ) associated with chronic infection cause long-term deficits in physical and cognitive development.

Epidemiology

The estimated worldwide prevalence of trichuriasis is 465 million, most commonly in poor, rural areas of the tropics and subtropics where disposal and treatment of human waste are inadequate. Children are more frequently infected than adults and more likely to have higher worm burdens. Humans are the only host.

Pathobiology

T. trichiura does not have a tissue migratory phase like A. lumbricoides and hookworm. After embryonated eggs are ingested orally, they hatch and release larvae into the proximal large intestine, where they undergo a series of molts before being carried passively to the transverse and descending colon. The adult worm’s narrow anterior end embeds in the columnar epithelium, while the posterior portion protrudes into the lumen. After mating, female worms expel unembryonated eggs into the feces, which are then passed into the environment, where they must embryonate in warm, moist soil to complete the life cycle. Adult worms can survive in the host for approximately 1.5 to 2 years. The period between ingestion of eggs and detection of eggs in feces is about 90 days.

Clinical Manifestations

Most T. trichiura infections are asymptomatic. Symptomatic disease occurs primarily in children because most heavy infections (>10,000 eggs per gram of feces) occur in this age group. Heavy infections can manifest as an acute dysentery or as a chronic colitis resembling inflammatory bowel disease with recurrent abdominal pain and diarrhea.

Diagnosis

Infection is diagnosed by microscopic identification of the typical barrel-shaped eggs with bipolar plugs in direct or concentrated smears of fecal specimens. PCR testing has been reported to be highly sensitive and specific by a few specialized laboratories but is not commercially available or approved as a diagnostic test.

Treatment

Prevention

As for A. lumbricoides and hookworm, control of trichuriasis in endemic areas consists of regular mass anthelminthic drug administration, primarily to preschool and school-aged children. Although the single doses of albendazole or mebendazole that are used in most mass drug administration programs worldwide are poorly effective for this intestinal nematode, their use is still recommended by the World Health Organization.

Prognosis

Chronic mucosal inflammation and edema of the colon and rectum can lead to protracted tenesmus that can result in rectal prolapse. Chronic Trichuris colitis can also lead to malnutrition, impaired growth, and anemia.

Epidemiology

E. vermicularis is found worldwide and is the most prevalent nematode infection in temperate climes. Transmission is frequent in primary schools and daycare centers.

Pathobiology

After ingestion, embryonated eggs hatch in the small intestine, where larvae develop into adult worms that migrate to the large intestine, where they mate. Gravid female worms emerge nightly from the anus to deposit large numbers of eggs (11,000 per worm) on the perianal and perineal skin, where they embryonate within 6 hours. If they are still on the skin, infective larvae are released and can migrate back through the anus into the rectum (retroinfection). Alternatively, autoinfection occurs when eggs are transferred to the mouth via scratching skin on which eggs have been deposited. Larvae may also migrate into the female genital tract and establish ectopic infection.

Clinical Manifestations

Although pinworm infections may be asymptomatic, perianal pruritus is the most common symptom and is due to an allergic response to worm proteins. The pruritus can be intense and result in chronic sleep deprivation in children. Rarely, adult E. vermicularis may precipitate appendicitis. When hatched larvae migrate into the female genital tract, vulvovaginitis, salpingitis, or peritonitis may develop.

Diagnosis

Pinworm infection is diagnosed by identifying the characteristic eggs through microscopic examination of a piece of cellophane tape applied to the perianal region immediately after waking in the morning. E. vermicularis eggs are oval and slightly flattened on one side. Eggs are not usually found in fecal samples. Repeated examination may be necessary.

Treatment

Prognosis

Enterobiasis usually does not result in severe manifestations, particularly in children, and it responds rapidly to appropriate treatment.

Epidemiology

S. stercoralis infection is endemic in the tropical and subtropical regions of sub-Saharan Africa, Asia, Latin America, and areas of Eastern and Southern Europe, with a worldwide prevalence of up to 100 million. In the United States, Strongyloides -related hospitalizations are rare, and infection is diagnosed most frequently in immigrants; however, strongyloidiasis is still endemic in parts of rural Appalachia. S. stercoralis can also be transmitted sexually through oral-anal contact, most often among men who have sex with men, or via transplantation of solid organs.

Pathobiology

Infection occurs when exposed skin comes in contact with free-living filariform larvae in soil contaminated with human feces. Like hookworm, larvae penetrate the skin, enter the vasculature, and migrate to the pulmonary capillaries, where they penetrate into the alveoli, ascend the bronchial tree to the pharynx, and are swallowed into the gastrointestinal tract. Further development into adult worms occurs in the upper small intestine, where parasites live embedded in the mucosa. Unlike most nematodes, S. stercoralis reproduces by parthenogenesis, with no apparent parasitic male worm present in the human host. Within 25 to 30 days after infection, female worms begin laying eggs, which rapidly hatch in the intestinal lumen and release noninfectious rhabditiform larvae that migrate to the colon and are excreted in feces. Alternatively, larvae may penetrate the colonic mucosa or perianal skin after migrating out of the anus and enter the circulation directly, a mechanism known as autoinfection that can lead to maintenance of parasitism in the host for decades.

In the soil, infectious filariform larvae can be produced either directly via transformation from rhabditiform larvae or indirectly from eggs released by free-living adult worms that have developed from rhabditiform larvae in warm, moist, sandy soil.

In immunologically competent individuals, infection does not usually result in symptomatic disease. However, serious complications may occur in individuals with cell-mediated immunodeficiency such as patients chronically taking corticosteroids, solid organ transplant recipients, patients with hematologic malignancies, or patients infected with human T-cell lymphotropic virus type 1. In these patients, the S. stercoralis autoinfection cycle can become amplified and lead to a hyperinfection syndrome with a large increase in the total worm burden in the infected person. Hyperinfection can lead to life-threatening dissemination of larvae and adult worms to aberrant sites such as the brain, pancreas, and kidneys. For unknown reasons, acquired immunodeficiency syndrome (AIDS) has not been associated with hyperinfection syndrome or with disseminated strongyloidiasis.