3. Life Cycle
INTRODUCTION — Ascaris lumbricoides, an intestinal roundworm, is one of the most common helminthic human infections worldwide. Highest prevalence in tropical and subtropical regions, and areas with inadequate sanitation. Ascariasis occurs in rural areas of the southeastern United States. In United States, ascariasis is the third most frequent helminth infection, exceeded only by hookworm and Trichuris trichiura (whipworm) . A. lumbricoides is the largest intestinal nematode of man. The female worms are larger than the males and can measure 40 cm in length and 6 mm in diameter. They are white or pink and are tapered at both ends. The epidemiology, life cycle and clinical features of ascariasis will be reviewed here.
EPIDEMIOLOGY — It is estimated that more than 1.4 billion people are infected with A. lumbricoides, representing 25 percent of the world population. A number of features account for its high prevalence including a ubiquitous distribution, the durability of eggs under a variety of environmental conditions, the high number of eggs produced per parasite, and poor socioeconomic conditions that facilitate its spread. Transmission is enhanced by the fact that individuals can be asymptomatically infected and can continue to shed eggs for years, yet prior infection does not confer protective immunity .
Although ascariasis occurs at all ages, it is most common in children 2 to 10 years old, and prevalence decreases over the age of 15 years. Infections tend to cluster in families, and worm burden correlates with the number of people living in a home . Infection rates for ascariasis have not been reported to be higher in patients infected with the human immunodeficiency virus (HIV) [4,5].
The highest prevalence of ascariasis occurs in tropical countries where warm, wet climates provide environmental conditions that favor year-round transmission of infection. This contrasts to the situation in dry areas where transmission is seasonal, occurring predominantly during the rainy months . The prevalence is also greatest in areas where suboptimal sanitation practices lead to increased contamination of soil and water. The majority of people with ascariasis live in Asia (73 percent), Africa (12 percent) and South America (8 percent), where some populations have infection rates as high as 95 percent [7,8]. In the United States the prevalence of infection decreased dramatically after the introduction of modern sanitation and waste treatment in the early 1900s . It is estimated that the current prevalence of A. lumbricoides in stool samples is approximately two percent in the United States, but it may be more than 30 percent in children between the ages of one to five years, particularly in rural areas of the South [10,11]. It is also seen in travelers from endemic areas .
Ova can survive in the environment for prolonged periods and prefer warm, shady, moist conditions under which they can survive for up to 10 years . The eggs are resistant to usual methods of chemical water purification but are removed by filtration or by boiling. Developing larvae will be destroyed by sunlight and desiccation. There is no significant animal reservoir, but A. suum, which infects pigs, is morphologically similar to A. lumbricoides, and the larval forms can occasionally infect humans.
Transmission — Transmission occurs mainly via ingestion of water or food (raw vegetables or fruit in particular) contaminated with A. lumbricoides eggs and occasionally via inhalation of contaminated dust. Children playing in contaminated soil may acquire the parasite from their hands. Transplacental migration of larvae has also occasionally been reported . Coinfection with other parasitic diseases occurs with some regularity because of similar predisposing factors for transmission [10,13].
LIFE CYCLE — Adult worms inhabit the lumen of the small intestine, usually in the jejunum or ileum. They have a life span of 10 months to 2 years and then are passed in the stool. When both female and male worms are present in the intestine, each female worm produces approximately 200,000 fertilized ova per day. When infections with only female worms occurs, infertile eggs that do not develop into the infectious stage are produced. With male-only worm infections, no eggs are formed.
The ova are oval, have a thick shell, a mamillated outer coat, and measure 45 to 70 Ķm by 35 to 50 Ķm. The ova are passed out in the feces, and embryos develop into infective second-stage larvae in the environment in two to four weeks (depending upon environmental conditions). When ingested by humans, the ova hatch in the small intestine and release larvae, which penetrate the intestinal wall and migrate hematogenously or via lymphatics to the heart and lungs. Occasionally, larvae migrate to sites other than the lungs, including to the kidney or brain.
Larvae usually reach the lungs by four days after ingestion of eggs. Within the alveoli of the lungs, the larvae mature over a period of approximately 10 days, then pass up via bronchi and the trachea, and are subsequently swallowed. Once back in the intestine, they mature into adult worms. Although the majority of worms are found in the jejunum, they may be found anywhere from the esophagus to the rectum. After approximately two to three months, gravid females will begin to produce ova which, when excreted, complete the cycle.
Adult worms do not multiply in the human host, so the number of adult worms per infected person relates to the degree of continued exposure to infectious eggs over time. Worm burdens of several hundred per individual are not uncommon in highly endemic areas, and case reports of more than 2,000 worms in individual children exist . However the number of eggs produced per female worm tends to decrease as the worm burden increases. It has been estimated that 9 x 10(14) eggs contaminate the soil per day worldwide .
Life Cycle Figure – Adult worms (1) live in the lumen of the small intestine. A female may produce approximately 200,000 eggs per day, which are passed with the feces (2). Unfertilized eggs may be ingested but are not infective. Fertile eggs embryonate and become infective after 18 days to several weeks (3), depending on the environmental conditions (optimum: moist, warm, shaded soil). After infective eggs are swallowed (4), the larvae hatch (5), invade the intestinal mucosa, and are carried via the portal, then systemic circulation to the lungs (6). The larvae mature further in the lungs (10 to 14 days), penetrate the alveolar walls, ascend the bronchial tree to the throat, and are swallowed (7). Upon reaching the small intestine, they develop into adult worms (1). Between 2 and 3 months are required from ingestion of the infective eggs to oviposition by the adult female. Adult worms can live 1 to 2 years. Source: CDC’s Parasite and Health Page about intestinal ascariasis.
CLINICAL FEATURES — The majority of infections with A. lumbricoides are asymptomatic. However, the burden of symptomatic disease worldwide is still relatively high because of the high prevalence of disease. Clinical disease is largely restricted to individuals with a high worm load . When symptoms do occur, they relate either to the larval migration stage or to the adult worm intestinal stage. Pathophysiologic mechanisms include
The symptoms and complications of infection can be classified into the following:
1. Pulmonary and hypersensitivity manifestations — Transient respiratory symptoms can occur in sensitized hosts during the stage of larval migration through the lungs. (See "Pulmonary manifestations of ascariasis"). Symptoms associated with the pneumonitis, which are known as Loffler's syndrome, tend to occur one to two weeks after ingestion of the eggs. The severity of symptoms tends to correlate with larval burden, but pulmonary symptoms are also less common in countries with continuous transmission of A. lumbricoides.
Urticaria and other symptoms related to hypersensitivity usually occur toward the end of the period of migration through the lungs.
2. Intestinal symptoms — Heavy infections with Ascaris are frequently believed to result in abdominal discomfort, anorexia, nausea and diarrhea. However, it has not been confirmed whether or not these non-specific symptoms can truly be attributed to ascariasis.
With relatively heavy infections, impaired absorption of dietary proteins, lactose and vitamin A has been noted, and steatorrhea may occur. One review concluded that Ascaris-free or treated children showed better nutritional status in terms of growth, lactose tolerance, vitamins A and C, and albumin levels than Ascaris-infected children based upon almost 20 years of published cross-sectional and intervention studies from Africa, Asia and South America . This review also found significant improvement in weight or height following therapy for ascariasis. However, other studies have not confirmed these conclusions, and the true effect of ascariasis on nutrition is still widely debated, especially as additional nutritional deficiencies commonly co-exist in infected children [16-23]. It has also been proposed that heavy infections may be associated with impaired cognitive development in school children [24,25].
3. Intestinal obstruction — A mass of worms can obstruct the bowel lumen in heavy Ascaris infection, leading to acute intestinal obstruction. The obstruction occurs most commonly at the ileocecal valve. Symptoms include colicky abdominal pain, vomiting and constipation. Vomitus may contain worms. Approximately 85 percent of obstructions occur in children between the ages of one and five years. Sometimes an abdominal mass that changes in size and location on serial examinations may be appreciated . Complications including volvulus, ileocecal intussusception, gangrene, and intestinal perforation occasionally result.
The overall incidence of obstruction is approximately 1 in 500 children. In endemic areas, it has been shown that between five and 35 percent of all cases of bowel obstruction are due to ascariasis . One review estimated the worm burden with intestinal obstruction to be >60 (and ten times higher in fatal cases) . Ascariasis is said to be the most common cause of acute abdominal surgical emergencies in certain countries including South Africa and Myanmar . In a recent meta-analysis of morbidity and mortality related to ascariasis, intestinal obstruction accounted for a mean of 72 percent of complications of the infection .
4. Hepatobiliary and pancreatic symptoms — Symptoms related to the migration of adult worms into the biliary tree can cause abdominal pain, biliary colic, acalculous cholecystitis, ascending cholangitis, obstructive jaundice, or bile duct perforation with peritonitis. Strictures of the biliary tree may occur . Hepatic abscesses can also result . Retained worm fragments can serve as a nidus for recurrent pyogenic cholangitis. The pancreatic duct may also be obstructed, leading to pancreatitis, and the appendix resulting in appendicitis. Occasionally, migrating adult worms emerge from the mouth, nose, lacrimal ducts, umbilicus or inguinal canal. High fever, diarrhea, spicy foods, anesthesia and other stresses have all been associated with an increased likelihood of worm migration .
In endemic countries such as India, ascariasis has been found to cause up to one-third of biliary and pancreatic disease [30,31]. In one study performed in Syria, 300 patients with biliary or pancreatic ascariasis were diagnosed by endoscopic retrograde cholangiopancreatography (ERCP) over a five-year period . Of these 300 patients, 98 percent presented with abdominal pain, 16 percent developed ascending cholangitis, 4 percent developed acute pancreatitis, and 1 percent developed obstructive jaundice. A previous cholecystectomy or endoscopic sphincterotomy had been performed in 80 percent. Endoscopic extraction of the worms, successful in all but two cases, led to rapid resolution of symptoms.
Complications associated with A. lumbricoides infections are fatal in up to five percent of cases. It is estimated that 20,000 deaths from ascariasis occur annually, primarily as a consequence of intestinal obstruction .
Ascaris lumbricoides in small intestine – Intestinal obstruction occurs when large masses of Ascaris accumulate. Source: Dr. Scott Smith’s lecture on GI Nematodes for “Parasites and Pestilence,” Stanford University.
q Microscopy — Characteristic eggs may be seen on direct examination of feces or following concentration techniques. However, eggs do not appear in the stool for at least 40 days after infection; thus, the main drawback of relying upon eggs in feces as the sole diagnostic marker for Ascaris infection is that an early diagnosis cannot be made, including during the phase of respiratory symptoms. In addition, no eggs will be present in stool if the infection is due to male worms only. Sometimes an adult worm is passed, usually per rectum. If an Ascaris worm is found in the feces, a stool specimen can be checked for eggs to document whether or not additional worms are present prior to instituting therapy .
Ascaris lumbricoides in stool – Wet mount of stool (x400) showing the ovum of ascaris lumbricoides. Source: UpToDate’s Ascariasis Graphics.
q Eosinophilia — Peripheral eosinophilia can be found, particularly during the phase of larval migration through the lungs but also sometimes at other stages of Ascaris infection . Eosinophil levels are usually in the range of 5 to 12 percent but can be as high as 30 to 50 percent. Serum levels of IgG and IgE are also often elevated during early infection.
q Imaging — In heavily infested individuals, particularly children, large collections of worms may be detectable on plain film of the abdomen. The mass of worms contrasts against the gas in the bowel, typically producing a "whirlpool" effect . Radiologic detection of adult worms is sometimes made by detecting elongated filling defects following barium meal examinations of the small bowel. The worms also sometimes ingest barium, in which case the alimentary canal appears as a white thread bisecting the length of the worm's body . Radiographs will also show when there is associated intestinal obstruction.
Biliary ascariasis – Cholangiogram obtained during endoscopic retrograde cholangiopancreatography shows a linear filling defect (arrow) that was later identified as an adult Ascaris lumbricoides worm. Source: UpToDate’s Ascariasis Graphics page.
q Ultrasound — Ultrasound examinations can help to diagnose hepatobiliary or pancreatic ascariasis. Single worms, bundles of worms, or a pseudotumor-like appearance may be seen . Individual body segments of worms may be visible, and on prolonged scanning, the worms will show curling movements . Computed tomographic (CT) scanning or magnetic resonance imaging (MRI) may also be used to identify worm(s) in the liver or bile ducts, but this is not usually necessary. Imaging the worm in cross-section gives a "bull's eye" appearance. When ascariasis involving the biliary tree or pancreatic duct is suspected, an ERCP will not only establish the diagnosis but also allows for the direct removal of the worm [32,37].
q Serology — Infected individuals make antibodies to A. lumbricoides which can be detected. However, serology is generally reserved for epidemiologic studies rather than in the diagnosis in a particular individual . IgG antibodies are not protective against infection . Antibodies to Ascaris also often cross react with antigens from other helminths.
Ascaris lumbricoides expelled following effective drug treatment. Source: Courtesy of Dr. Tom Nutman, NIH.
* Pyrantel pamoate — Pyrantel pamoate (11 mg/kg up to a maximum of 1 g) is administered as a single dose. Adverse effects include gastrointestinal (GI) disturbances, headaches, rash, and fever. Parasite immobilization and death occur, although this happens slowly and complete clearance of the worm from the GI tract may take up to three days. Efficacy varies with worm load, but single dose therapy is approximately 90 percent effective in eradicating adult worms .
* Mebendazole — Mebendazole (100 mg BID for 3 days or 500 mg as a single dose) is an alternative. Adverse effects include transient GI discomfort, headache, and rarely leukopenia. The three-day regimen is approximately 95 percent effective, and the single dose seems to have similar results.
* Albendazole — A single dose of albendazole (400 mg) is effective in almost 100 percent of cases, although reinfection commonly occurs . Albendazole causes the same adverse effects as mebendazole.
* Ivermectin — Ivermectin causes paralysis of adult worms and is approximately as effective as other available therapies but is not generally used.
* Piperazine citrate — Piperazine citrate (50 to 75 mg/kg QD up to a maximum of 3.5 g for 2 days) was a frequent treatment regimen, but it is now being withdrawn from the market in many developed countries because the other alternatives are less toxic and more efficacious. However, it may still be recommended when there is suspected intestinal or biliary obstruction since this drug paralyzes worms to aid expulsion.
* Levamisole — Levamisole (150 mg for adults and 5 mg/kg for children) is safe and is effective in 77 to 96 percent of cases of ascariasis.
Choice of therapy — The mainstays of treatment currently are the benzimidazoles, mebendazole and albendazole. However, they should not be given during pregnancy because of possible teratogenic effects. Thus, pyrantel pamoate should be used in pregnancy. In a randomized study conducted among 2,294 children aged 6 to 12 years in Zanzibar, single dose mebendazole and albendazole were both found to have efficacies greater than 97 percent . Similar results with both drugs and good tolerability have also been observed in other studies [41-43].
Follow-up — All of these therapies act against the adult worm but not the larvae. Following therapy, patients should be reevaluated at two to three months to ensure that no eggs are detectable, either because of inadequate elimination of adult worms or because of reinfection. Reinfection occurs frequently; more than 80 percent of individuals in some endemic areas become reinfected within six months . Evaluation of other family members should be entertained whenever the diagnosis is made because of the propensity of the infection to cluster in families [10,12].
Supportive care — In addition to specific anthelminthic therapy, supportive therapy for complications of ascariasis may be required, including potential surgical intervention for intraabdominal complications. In biliary infections, conservative therapy with anthelminthics, often combined with antispasmodics, is often successful. However, surgical or endoscopic interventions may be required.
Since pulmonary ascariasis is a self-limited disease, symptomatic alleviation of wheeze and cough with inhaled bronchodilators can be instituted. Occasionally, systemic corticosteroids may be required for symptoms. Following symptomatic therapy, standard therapy for intestinal ascariasis can be given after the worms have developed to maturity in the small intestine . Anthelminth therapy is not usually given at the time of pulmonary symptoms because dying larvae may do more harm than migrating ones.
Biliary ascariasis – An adult Ascaris lumbricoides worm protruding from the major papilla is grasped with forceps during endoscopic retrograde cholangiopancreatography. Source: UpToDate’s Ascariasis Graphics page.
PREVENTION — Prevention of reinfection poses a substantial problem since Ascaris parasites are abundant in soil. Good sanitation to prevent fecal contamination of soil is required. An education program advising against the use of human feces as a fertilizer is also needed in some areas. Soil treatments have been attempted but are generally not practical.
Mass treatments with single dose mebendazole or albendazole for all school-age children every three to four months has been used in some communities. This serves the dual function of treating the children and reducing the overall worm burden in the community. Indeed, mass community therapy has been shown to reduce Ascaris burden and transmission, although it has a greater effect on the intensity of infection than on the overall prevalence [44-47]. This approach has been shown to be cost-effective . Because reinfections occur so frequently, shorter intervals between treatments have been found to be preferable. Targeted treatment helps control the morbidity of infection but does not have a substantial effect on transmission [44,49,50]. In a large randomized trial of school-based deworming performed in Zanzibar, for example, single dose mebendazole, given either twice or three times a year, decreased intensity of A. lumbricoides infection by 63 and 97 percent, respectively, compared to control children who received no mebendazole .
CREDITS — This website has been adapted by Jessika Lora from Karin Leder and Peter F. Weller’s UpToDate review of ascariasis.
“UpToDate performs a continuous review of over 330 journals and other resources. Updates are added as important new information is published. The literature review for version 13.1 is current through December 2004. The next version of UpToDate (13.2) will be released in June 2005.”