Intestinal Nematodes

Epidemiology

Ascariasis is the most common helminth infection in humans, with over 400 million people infected worldwide. ^, Morbidity is most apparent in children who harbor the heaviest burden of infections. A. lumbricoides eggs are resistant to a wide array of environmental stresses allowing for ubiquitous contamination of environments with poor sanitation and waste management. ^, Ascariasis still occurs in the US as an imported infection, usually in recent immigrants from Latin America and Asia, and in internationally adopted children. ^{, ,} However, ascariasis likely remains an autochthonous infection in the southeastern US, where the rate of infection in children has historically ranged from 2.3% to 49%. Additionally, transmission of Ascaris suum , the porcine roundworm, which is morphologically indistinguishable from human roundworm and genetically similar, also can infect humans, causing disease typically in children living near pig farms. ^,

Chronic ascariasis in childhood can be associated with impaired physical growth and cognitive development, which in some cases can be linked to vitamin A and other micronutrient malabsorption as well as protein-calorie malnutrition. Young children also are more susceptible to life-threatening complications such as intestinal obstruction, perforation, and peritonitis. Globally, intestinal and biliary tract obstruction caused by Ascaris accounts for 10,000–100,000 deaths a year, mostly in children. ^, In low- and middle-income countries, the rate of complications secondary to ascariasis ranges from 11% to 67%, with intestinal or biliary tract obstruction the most common serious sequela. There have been case reports of transplacentally acquired neonatal ascariasis, but the prevalence of this mode of transmission remains unclear. ^,

The life cycle of A. lumbricoides in humans begins with ingestion of embryonated eggs that have been deposited in moist soil. The acidic environment in the stomach followed by the bile salts and the alkaline pH of the small intestine aids in larvae hatching. Emerging third-stage larvae penetrate the bowel wall and ultimately invade the microcirculation of the lamina propria. Once in the circulatory system, larvae are carried to the liver through the portal veins and eventually are swept into the pulmonary vasculature, where they lodge in capillaries and rupture into the alveolar space. While in the lungs, third-stage larvae molt, shedding the outer chitin layer, into fourth-stage larvae. Fourth-stage larvae penetrate through the pulmonary epithelium into the bronchi, ascending the bronchi to the trachea; larvae are swallowed and again migrate to the small intestine. Ascaris larvae mature into sexually differentiated adults in the lumen of the small bowel, mate, and begin laying eggs. Adult female worms produce over 200,000 eggs per day and can live up to 2 years in the human host.

Clinical Manifestations

Illness associated with ascariasis can be attributed to the migration of both larvae and adult worms. As larvae migrate through the lung parenchyma, they cause both mechanical and immune-mediated damage. Pulmonary microhemorrhages from ruptured alveolar capillaries result in inflammation and fluid exudate. Neutrophils and eosinophils are recruited to the lung in response to proteins released by the migrating larvae. ^, Pulmonary infiltrates in association with cough, dyspnea, wheezing, and mild hemoptysis (Löeffler pneumonia) can occur and last up to 2 weeks. Children with ascariasis have increased risk of asthma and atopy and, as such, ascariasis may be a leading cause of asthma worldwide. The intensity of illness caused by migrating larvae is proportional to larval numbers, with lightly infected people having fewer pulmonary symptoms. In rare instances, adult worms from the intestines can migrate into the airways and cause airway obstructed respiratory distress.

Symptoms associated with the presence of adult Ascaris worms in the small bowel include epigastric pain and diffuse abdominal discomfort. Because adult worms can grow to 35 cm in length, heavy infestations can result in acute intestinal obstruction and perforation, especially in the region of the ileum, which requires emergency medical or surgical intervention ( Fig. 276.2 ). ^{, ,} Migration of adult worms into the biliary tree, and then to the liver or pancreas, can precipitate acute cholangitis, cholecystitis, hepatitis, pancreatitis, and hepatic abscess if the intrahepatic ducts are obstructed.

Chronic ascariasis has been associated with malnutrition, which is caused by malabsorption of dietary protein, fat, and vitamin A. The pathogenesis of malabsorption of nutrients is likely multifactorial. ^{, ,} Investigators have postulated that adult worms successfully compete for nutrients by secreting a variety of enzymes and protease inhibitors into the proximal region of the small intestine. Whether the physical and mental growth restriction syndromes associated with chronic ascariasis in childhood have a purely nutritional basis remains unknown. Furthermore, Ascaris infection frequently occurs in the setting of infection with other intestinal nematodes, especially Trichuris and hookworm, thus making it difficult to ascribe long-term sequelae to an individual parasitic species.

Laboratory Findings and Diagnosis

The diagnosis of Ascaris infection is best established by examination of stool for characteristic ova using light microscopy ( Fig. 276.1 ). The Kato-Katz stool preparation method is low-cost and semi-quantitative which correlates with worm burden. Repeat testing and multiple slides may be needed due to daily fluctuations in egg release, and an experienced microscopist is required to increase sensitivity. The use of concentration techniques may aid in identification of Ascaris eggs, particularly in low burden disease. In areas with low worm burden, molecular techniques, such as quantitative polymerase chain reaction (qPCR), have been beneficial to determine worm burden. For identification and quantitation of ascariasis, qPCR has been shown to have increased precision compared to Kato-Katz. ^, However, the cost and the need for additional equipment and an energy source remain barriers to the use of qPCR in endemic regions.

When migration of Ascaris larvae through the lungs is associated with peripheral blood eosinophilia and pulmonary infiltrates on a chest radiograph, examination of sputum can reveal larvae, eosinophils, and Charcot-Leyden crystals. The differential diagnosis includes other causes of parasitic pneumonia, including strongyloidiasis, toxocariasis (visceral larva migrans), hookworm infection, and filariasis (tropical pulmonary eosinophilia).

In areas endemic for A. lumbricoides, any child manifesting acute abdominal symptoms consistent with intestinal obstruction or perforation should be evaluated for ascariasis. Occasionally, an adult worm is present in vomitus. Abdominal radiographs after barium administration can diagnosis A. lumbricoides as coiled radiolucent filling defect within the intestine. Similarly, computed tomography (CT) with oral contrast may demonstrate an elongated linear filling defect within the lumen of the intestines. Using ultrasonography, adult Ascaris worms appear as a “linear intraluminal mass” longitudinally or as a “target” size on cross section. Endoscopic retrograde cholangiopancreatography (ERCP) and ultrasonography can be helpful in identifying adult Ascaris worms in the hepatobiliary tree. ^{, ,} ERCP can be used for removal of the adult worm from the biliary tract. ^, Occasionally, however, the diagnosis of intestinal ascariasis is made during exploratory laparotomy typically performed due to intestinal obstruction of unknown etiology. ^,

Treatment

Benzimidazoles, such as mebendazole (100 mg twice a day for 3 days or 500 mg once) and albendazole (400 mg in a single dose), are effective for treatment of intestinal ascariasis, with cure rates >90%. ^{, ,} Because of their potential teratogenic and tumorigenic effects seen in animal models, but not demonstrated in human studies to date, benzimidazoles generally are not given to children aged <12 months or women during their first trimester of pregnancy. However, extensive experience with the use of these agents in children supports that a reduced dose of albendazole (200 mg) in a single dose given to children 12–24 months of age, or even children <12 months of age, is not problematic and should be used when necessary. Additionally, pregnant women after their first trimester of pregnancy can also be treated with benzimidazoles at standard dosing. For this reason, benzimidazoles increasingly are being distributed in low- and middle-income countries with heavy disease burdens for treatment and for preventive chemotherapy as part of MDA programs. Side effects are rare, with mild gastrointestinal symptoms, dizziness, headache, transaminitis, and leukopenia reported. ^, Benzmidazoles should be taken with a high fat meal. Reports of benzimidazole resistance have emerged for Ascaris lumbricoides secondary to a mutation in the β-tubulin isotype-1 gene, similar to reports in other nematodes. Alternative therapies include ivermectin (150–200 μg/kg once) which has been shown to be highly effective against ascariasis; however, safety data for the use of ivermectin in children weighing <15 kg and pregnant women limits its widespread use and it is not approved by the US Food and Drug Administration for ascariasis. Nitazoxanide is comparable to albendazole for treatment of Ascaris infections and is approved for use in children aged 12 months. The recommended dose is 100 mg (5 mL) twice a day for children 12–47 months of age, 200 mg (10 mL) twice a day for children 4–11 years of age, and 500 mg twice a day for older children and adults, completing a 3-day course; bioavailability is significantly increased when taken with food. Pyrantel pamoate (11 mg/kg up to maximum 1 g/day for 3 days) is an additional suitable alternative. In some heavily infected children, malnutrition, steatorrhea, and growth restriction are partially reversible with treatment; however, there remains conflicting data on the long-term impact of treatment on chronic morbidity.

In the case of intestinal obstruction, mineral oil or gastrografin (a solution of diatrizoate meglumine and diatrizoate sodium) given orally or by nasogastric tube also can cause relaxation of the obstructing bolus of worms and enhance expulsion; however, it is unclear if use of gastrografin reduces need for laparotomy. Standard supportive measures for treatment of small bowel obstruction also should be administered, including intravenous hydration, nasogastric suctioning, and monitoring of electrolyte status. Laparotomy to remove the adult worm bolus should be undertaken in patients who do not respond to therapy with anthelmintic drugs.

Prevention

Prevention of ascariasis requires elimination of contact with soil contaminated by eggs. Although Ascaris eggs are killed by prolonged exposure to sunlight or temperatures >40°C, they can survive in extremely cold temperatures for many months and are resistant to many chemical disinfectants. Ascaris eggs survive in temperate climates and urban environments.

Enhanced diagnostics and effective anthelminthic treatment in combination with WASH programs is the most reliable means of combating widespread Ascaris transmission within a community. In endemic areas where the prevalence of infection with intestinal nematodes is >50%, preventive chemotherapy using benzimidazole agents should be administered to high risk populations (children aged >12 months, non-pregnant adolescent girls, and non-pregnant women of reproductive age) twice yearly as part of a targeted deworming program; prevalence of 20% to 49% requires annual treatment within the same high-risk groups. However, the effects of a single intervention are likely to be short-term given the inevitability of reinfection in endemic regions. Because ascariasis is an infection that is associated with poverty and poor sanitation, improved water, sanitation, and hygiene, together with sustained economic growth, are requirements for long-term parasite control and potential for elimination.