Intestinal nematodes have a worldwide distribution but are endemic in tropical and subtropical regions. Of the six nematodes commonly infecting humans, Ascaris is a cause of significant surgical morbidity and mortality. In some endemic regions, ascariasis is the most common cause of intestinal obstruction in children and of biliary disease in both children and adults. Other intestinal nematodes infect man incidentally, e.g. infection by larvae of Anisakis sp. causes anisakiasis, a rare infection in Japan, Holland, and Scandinavia where raw fish is eaten, and causes haematemesis by burrowing into gastric mucosa. Capillariasis caused by C. philippinensis, acquired from fresh-water fish, causes severe intestinal symptoms, and C. hepatica infects the liver. It is found mainly in rodents.

The World Health Organization estimates that 1.3 billion persons, or a quarter of the human race, are infected by this nematode helminth. Every year up to a million cases of clinical disease are recorded and between 8000 and 100000 infected children die from intestinal obstruction and other abdominal complications of ascariasis.

Man is infected following ingestion of mature eggs in soil-contaminated food or drink. The outer coats are digested in the stomach and the invasive larvae are released in the duodenum. They penetrate the mucosa and enter the mesenteric venous radicles or lymphatics, passing through the portal vein into the liver. They then pass through the hepatic veins to the vena cava and right heart into the pulmonary circulation. There they penetrate the alveolar walls and migrate up the bronchioles and trachea into the pharynx and oesophagus, where they are swallowed again.

During the migration, which lasts 14 days, the larva grows to about 2 mm in length and moults twice. Further growth and maturation in the jejunum results in the production of adult male and female worms which then normally settle in the small intestine. Some 60 to 75 days after ingestion of infective eggs, the new gravid female worm begins to lay its own eggs. The mean life-span of an adult worm is 1 to 2 years, after which it is spontaneously expelled. In endemic areas, however, there is repeated reinfection, resulting in heavy worm loads, especially in children.

The adult worms live and mate in the human jejunum and mid-ileum. The female is 20 to 49 cm long and 3 to 6 mm wide; the male is 15 to 30 cm long and 2 to 4 mm wide. Each worm is pinkish-white, rounded and tense with a striated cuticular surface and two longitudinal streaks. The blunt anterior end has three lips. The vulva opens ventrally in the female and there are two copulatory spicules at the centrally curved posterior end of the male.

Ascaris feeds on the host's intestinal contents and is equipped with its own battery of digestive enzymes, including amylase, protease, and lipase. The adult worms are facultative anaerobes with a glycogen consumption of 1.3 g/100 g body weight/day. The larval stages have anaerobic metabolism, while the infective eggs in the soil are dormant. Amino acids required for egg production are partly obtained from the gut and partly synthesized by the ovaries. Each female lays up to 240000 eggs per day. These are passed with stool into the soil to complete the life-cycle. The eggs may lie dormant for a long time if the soil is moist. There are no intermediate hosts.

The worm has to survive a hostile digestive, mechanical, and immunological environment in man. The mechanisms by which this is achieved, many of which have only recently been discovered, have largely been elucidated from experimental work with Ascaris suum infection of pigs. The adult worm is not attached to the intestinal mucosa but is braced most of the time by its own muscle power against the intestinal wall and peristaltic activity. Its spindle shape and spiral movements facilitate forward motion and entry into small orifices such as the ampulla of Vater. The cuticle, which covers the entire body and its invaginations, seems to play a major role in protecting the worm. It is a secreted multilayered structure of collagen, hyaluronic acid, chondroitin sulphate and mucopolysaccharides and is both chemically and physically resistant. The collagens have many of the characteristics of vertebrate type IV collagens and may be involved in the parasite's molecular mimicry of the host as a mechanism of immune evasion. A multigene family coding for these collagens has recently been described.

The worm also appears to escape digestion by elaborating families of iso-inhibitor proteins. These have been shown in A. suum to inactivate the host's pancreatic proteases, chymotrypsin, elastase, trypsin, and carboxypeptidases A and B. Inhibitors of pepsin have also been reported, one of which is an aspartyl protease inhibitor. Such protease inhibitors are critical to parasite survival and perhaps to their species specificity and are now being explored as possible avenues for parasite control.

Although the adult worm manages to parasitize man successfully there is evidence for an immune response to various stages of the worm and also for the development of partial immunity. The predominant immunological response to Ascaris in man appears to involve eosinophils and IgE antibodies; levels of IgG and IgD are increased to a lesser extent, and IgA and IgM levels are not increased. Ascaris antigens released during larval moulting evoke an immune response, with production of IgG antibody. During passage through the intestinal mucosa, some larvae are immobilized, covered with eosinophils, and destroyed. Similarly in the liver sinusoids, some larvae are killed by infiltrating eosinophils, neutrophils, and histiocytes, which form granulomatous pseudotubercles (the Splendore-Hoeppli phenomenon). This represents an eosinophil-mediated antibody-dependent cell mediated cytotoxicity reaction. The cytokine IL-5 plays a role in preparing eosinophils for this function. In the lung, there may be serous alveolar exudate, peribronchial eosinophilic infiltrate, and bronchial spasm with increased mucus secretion. This manifests clinically as Loeffler's syndrome, during which a chest radiograph will show diffuse mottling. The degree of this reaction is related to the number of larvae migrating simultaneously. The frequency of this immediate-type hypersensitivity reaction is much less in regions where there is continuous infection than where the infection is seasonal.

Although IgE antibodies to Ascaris antigens are produced by infected persons, there are relatively few reports of severe anaphylactic reaction in such patients. In contrast, laboratory personnel become extremely sensitive to volatile allergens of Ascaris worms and may respond with bronchial asthma, angioneurotic oedema, urticaria, and sometimes gastrointestinal symptoms.

There is some evidence in man for partial immunity acquired against helminths. In endemic areas, the prevalence of infection declines with age while the presence of antibodies in the serum increases. In a recent study from a village in Papua New Guinea, 95 per cent of children were infected compared wiith only 21 per cent of adults. Antibody levels in the adults were much higher than in the adults from another village with a lower intensity of childhood infection. This suggests that in adults with low egg counts and high antibody titres, although continuous reinfection may occur, immunity prevents the worms becoming established. Heavy and continuous exposure engenders resistance against superinfection rather than rejection of all worms.

Some studies in rodent infections have recently suggested, however, that the IgE and increased eosinophil levels are not entirely part of the specific immune response to the helminth. The worm appears preferentially to activate the TH2 cell pathway. TH2 cells then produce the cytokines IL-4 and IL-5, which in turn stimulate the production, respectively, of non-parasite-specific IgE and eosinophils. This TH2 response, significantly, also down-regulates TH1 responses which, by producing &ggr;-interferon and IL-2, might actually have been more effective in bringing about parasite destruction. Current vaccine studies are aimed at understanding and then overcoming this strategy of large multicellular parasites to selectively trigger the TH2 pathway.

Recent biochemical studies have shown that the parasite can also protect itself from attack by toxic molecules such as oxygen free radicals, nitric oxide, and carbonyls, released by activated inflammatory cells, by producing a battery of its own defensive enzymes (catalase, superoxide dismutase, glutathione peroxidase, and carbonyl reductase) which neutralize the toxic molecules. Current research is aimed at upsetting this balance by developing agents that would inactivate the parasite's defensive enzymes.

Most ascaris infections are unnoticed by the host until an adult worm is passed in the faeces or through the mouth. However, a patient infected with many worms may complain of vague central abdominal pains, anorexia, intermittent loose stools, and occasional vomiting. The pain in adults may be epigastric, resembling chronic peptic ulcer pains.

Partial obstruction of the intestines by intertwining of the worms may cause intestinal colic, nausea and vomiting and fever; a palpable mobile abdominal mass may be present. Complete intestinal obstruction usually occurs when a tangled mass of worms is impacted in the distal ileum. This is on occasion precipitated by the use of antihelminths in a patient with partial obstruction. The patient develops severe colicky abdominal pain with vomiting and obstipation. The abdomen is distended with hyperactive bowel sounds often with visible peristalsis and tenderness. The affected segment may act as a fixed point on which the rest of the bowel twists, causing a volvulus; the closed loop loaded with the worms is thus prone to strangulation and bowel rupture unless prompt laparotomy is performed. Alternatively, intense spasm of the bowel around an obstructing ball of worms may be advanced as the leading point of an ileocaecal intussusception which may also progress to bowel ischaemia if not relieved. Sometimes the worm obstructs the appendix causing acute appendicitis; the worm may also perforate through the appendix into the peritoneal cavity.

In an endemic area, ascariasis is always considered in the differential diagnosis of intestinal obstruction. The suspicion is strong in patients with a recent history of passing a worm or of using a purgative or vermifuge before developing the features of intestinal obstruction. Such patients are admitted to hospital for evaluation.

A plain abdominal radiograph may show the worms along with air - fluid levels and dilated bowel loops. Abdominal ultrasound may also show a mixed echogenic mass, provided the distended loops are not in the way. In doubtful cases a barium meal with follow through will outline the worms, which may also ingest some of the barium.

Oral feeds are stopped, and intravenous fluids and electrolytes begun. A nasogastric tube is inserted and an antispasmodic such as meperidine or hyoscine butylbromide (buscopan) is given intravenously in order to relax the bowel and allow the worms to disentangle and move into the colon, from where they are likely to be expelled. An antihelminthic such as piperazine or pyrantel is given (via the tube or by mouth with the tube clamped) only after the attack has subsided. This is done so as not to paralyse the worms in the ileum where the paralysed tangled mass could cause complete obstruction. A large majority of affected patients respond promptly to this regimen by passing numerous worms rectally. Digital disimpaction may facilitate worm evacuation. In some stable and well-hydrated children, diatrizoate meglumine (gastrograffin), which causes osmotic diarrhoea, has been given through the nasogastric tube and has resulted in worm expulsion. Patients are discharged when normal bowel function has returned.

This regimen is, however, likely to fail when bowel obstruction is complicated by volvulus or intussusception. Prompt laparotomy is indicated after appropriate resuscitation in such patients and in those with advanced disease suggestive of strangulated or gangrenous intestinal obstruction. At laparotomy, if the bowel is not gangrenous, and whenever feasible, the worms are manually disentangled and massaged into the colon from where expulsion follows the postoperative administration of an antihelminth. Otherwise, a judicious enterotomy is made and the worms extracted with minimal spillage of gut contents (Fig. 1) 2672. We do not recommend the practice of resecting viable bowel with the contained worms. However, when the bowel segment is not viable, resection is performed with end-to-end anastomosis. Whenever the bowel is opened or resected, it is important to remove all the worms: a remaining worm may exit through the suture line postoperatively.

In endemic regions, ascariasis is the cause of up to 25 per cent of intestinal obstructions. It is estimated that in the tropics, 11 per cent of paediatric laparotomies are indicated for complicated intestinal ascariasis. In a children's hospital in South Africa 12.8 per cent of all acute abdominal emergencies were caused by ascariasis; most of these were managed non-operatively. In another South African series, 22 of 29 children with volvulus required bowel resection. Five (17 per cent) of the 29 died from the complications of gangrenous bowel, endotoxaemia, or anastomotic failure.

In a report from Colombia, ascariasis accounted for 14.4 per cent of 500 children admitted with an acute abdomen to a paediatric surgery unit. Among 107 children with ascaris intestinal obstruction, simple obstruction was present in 34, volvulus with or without gangrene in 63, and intussusception in 7. Because of late presentation, bowel resection was required in 68 children, of whom eight (12 per cent) died. Of the 51 without bowel resection only two (4 per cent) died. Ten other children presented with appendiceal perforation; of these, one died following appendectomy.

Migration of an adult ascaris through the sphincter of Oddi into the common bile duct leads to biliary ascariasis. Worm migration may be triggered by some drugs, anaesthetic agents, antihelminthics, fever, or spicy foods. Entry into the bile duct is facilitated in patients with a previous sphincterotomy. The worm may spontaneously return to the duodenum causing no symptoms at all. However, a female worm may be stranded in the bile duct or gallbladder where it dies after laying some eggs. Such eggs and degenerating cuticular fragments may cause cholangitis, with or without secondary bacterial infection, or become the nidus for gallstones. Several worms invading the bile duct are more likely to block the cystic duct and cause biliary colic or acalculous cholecystitis. Further ascent into the hepatic ducts is associated with acute cholangitis, and an abscess may form within the intrahepatic ducts and liver parenchyma.

In endemic regions, biliary ascariasis may be the most common cause of biliary disease in both children and adults. The frequency and clinical pattern varies in different parts of the tropics; children are more frequently described in Latin America but more adult cases have been reported from India. The symptoms of hepatobiliary ascariasis are variable. Recurrent right hypochondrial pain associated with nausea and vomiting is typical for biliary colic. The patient with a sudden, intense right upper quadrant pain associated with a low-grade fever (37.5°C) and bilious vomiting (sometimes containing a worm) is more likely to have acute cholecystitis. The invading worms carry some enteric flora into the bile duct and cholangitis is manifested by a high-grade fever (38 - 40°C), jaundice and a palpable gallbladder. The liver is enlarged and tender, serum bilirubin and alkaline phosphatase levels are elevated, and there is a marked leucocytosis. If untreated, septicaemia and endotoxic shock may supervene. A liver abscess is associated with high fever hepatomegaly, and exquisite intercostal tenderness.

Biliary ascariasis can be diagnosed with abdominal ultrasonography. Dilatation of the biliary tree due to obstructing worms can be shown. The cross-section of the bile duct containing a worm shows a bullseye configuration while the longitudinal plane shows an echogenic strip with a central longitudinal anechogenic tube. The spaghetti sign is caused by several worms being imaged at a time.

A CT scan will also show the worm in the dilated bile duct or gallbladder and is useful in locating a liver abscess. The most helpful investigation, however, is duodenoscopy with endoscopic retrograde cholangiopancreatography, which provides for both diagnosis and therapy. The worms can be seen in the duodenum or entering or leaving the ampulla of Vater and can be removed. Bile samples can be obtained and examined for Ascaris eggs or cultured for bacteria. The contrast study will show the position and number of worms. Especially when cholangitis is present, worms can be removed using forceps, Dormia basket, or balloon-tipped catheter. A nasobiliary catheter may be left in place for decompression.

As for intestinal obstruction, fluids are given and nasogastric suction performed while antispasmodics are given intravenously to relax the sphincter of Oddi. This facilitates the return of the worms into the small intestine. At the same time intravenous antibiotics are given. After the acute attack subsides, an antihelminthic drug is given in order to expel the worms from the intestines. Most patients improve on this regimen. If not, duodenoscopy is performed and the worms extracted from the ampulla or bile ducts, as described above. This provides rapid relief of symptoms. Recurrence of symptoms usually signifies reinfection by worms and the treatment regimen may be repeated as necessary.

Very rarely, non-operative and endoscopic management may fail. Exploration of the common bile duct is required in such instances, especially if cholangitis has resulted in bile duct stricture. It may be prudent to perform a wide bilio-enteric anastomosis with the expectation that any subsequently invading Ascaris will be free to move in and out of the biliary tree.

In the Columbian series, biliary ascariasis presented in 19 children under the age of 12. The majority responded to non-operative management. In a recent cohort of 500 Indian patients from Kashmir, the mean age was 35 years and the mean duration of illness was 6 years. Biliary colic was present in 280; 64 presented with cholecystitis; 121 with cholangitis and four with liver abscess. Diagnosis was confirmed by ultrasonography and, where necessary, endoscopic retrograde cholangiopancreatography. All patients were initially treated palliatively and antihelminthic drug treatment was given after the acute symptoms had subsided. Extraction of worms from the duodenum, ampulla, and bile ducts led to rapid relief of biliary colic. In 12 patients, dead worms were removed endoscopically or surgically from the bile ducts. During the follow-up period, seven patients required surgery for the removal of intrahepatic and bile duct stones which were found to be soft pigment stones containing a nidus of Ascaris segments.

One of the least commonly diagnosed, but often fatal, complications of ascariasis is acute pancreatitis caused by worm impaction in the ampulla and pancreatic duct. The pain is usually epigastric with radiation to the back and is associated with vomiting and fever. Serum amylase and alkaline phosphatase levels are usually elevated. Ultrasonography may reveal an enlarged echo-poor pancreas, but the limitation of sonography in the diagnosis of pancreatic disease is now well recognized. Emergency endoscopic retrograde cholangiopancreatography is indicated in all such patients because it shows the correct aetiology and allows prompt extraction of the obstructing worm.

In the series from Kashmir, 31 of 500 patients presented with acute pancreatitis, which was severe in three cases. Many of the patients improved on non-operative management, but 16 required worm extraction. One of these died from haemorrhagic pancreatitis despite laparotomy and extraction of four worms from the pancreatic duct and seven from the bile duct.

In an instructive case report from Europe, a 66-year-old Swiss patient with no history of alcohol abuse or gallstones died from fulminant pancreatitis. His serum bilirubin and alkaline phosphatase levels had been normal and emergency ultrasound had not shown biliary dilatation. Endoscopic retrograde cholangiopancreatography had not been performed. At necropsy, an Ascaris worm was found impacted in the ampulla of Vater and pancreatic duct. In view of modern world travel and population migration, clinicians even in non-endemic regions of the world need to be aware of the lethal consequence of undiagnosed Ascaris pancreatitis and to consider it in their differential diagnosis.

The larval form in the pulmonary circulation may fail to penetrate into an alveolus but may enter a pulmonary vein tributary and thence be carried into the left side of the heart. From there it can reach any part of the arterial circulation, including the brain and splanchnic bed. Immature worms have exited from the nasolachrymal duct, for instance.

The adult worm in the jejunum may migrate proximally into the duodenum (Fig. 2) 2673 and stomach and cause peptic ulcer-like symptoms and gastric outlet obstruction. It may ascend the oesophagus into the pharynx and be vomited or be aspirated into the trachea and cause asphyxia, which may be fatal (Fig. 3) 2674. It may descend further down into the bronchus to cause atelectasis or lung abscess. It may pass into the nasopharynx and exit through the nostrils or from the oropharynx and through the eustachian tube into the middle ear and through a perforated tympanum to the auditory canal.

Worms that have caused liver abscess may penetrate the diaphragm into the pleura, causing an empyema. From the liver the worm may also break into the hepatic veins or vena cava and be carried to the right heart and be embolized to the pulmonary artery. The worm may penetrate a Meckel's diverticulum or exit via a patent omphalomesenteric duct at the umbilicus. An occasional worm may perforate a bowel wall, which has perhaps been weakened by typhoid or tuberculosis, to reach the peritoneal cavity where it dies leaving remnants and eggs around which large granulomatous masses develop: these clinically resemble abdominal tuberculosis, schistosomiasis, or lymphoma. Other locations reached by worms include the renal pelvis and urinary bladder, the fallopian tubes, and the uterus via abnormal fistulae.

The environmental conditions and cultural practices that favour infection by the other intestinal nematodes are similar to those required by Ascaris.

In endemic regions, the most intense infections occur in children, many of whom live on a borderline or inadequate diet. Polyparasitism and other infections add up to a major disease burden whose sequelae include anaemia, malabsorption, protein energy malnutrition, growth retardation, delayed puberty, and impairment of cognition and of academic performance. Public health control measures for prevention of infection are very important, although many safe and effective drugs are now available for treatment. Improved economic development has the greatest promise in the long term. Effective vaccines, when they become available, may have a future role.

Hookworms are usually considered together. Ancylostoma is more prevalent in temperate lands, while Necator is perennial in the tropics and subtropics. The major clinical disease is blood loss and iron deficiency anaemia due to the ingestion of blood and the complications of mucosal damage. In patients already on a marginal diet, a heavy worm load leads to chronic anaemia which may be associated with impaired learning in children, pregnancy complications, and heart failure.

Strongyloidiasis may persist for decades because of its capacity for autoinfection. Recurrent disease is seen in European veterans of the Second World War who served in Asia 40 years previously. The clinical triad of urticaria, epigastric pain, and watery diarrhoea may be disabling. Hyperinfection syndrome may occur when the host - parasite balance is upset by serious illness or therapy which lowers the immune competence of the host, such as major burns, lymphoma, leukaemia, other malignancies, corticosteroid therapy for ulcerative colitis or idiopathic thrombocytopenia, and immunosuppressive therapy for organ transplantation. In these circumstances rhabditidiform larvae convert to filariform larvae within the intestines and massive autoinfection (either internal (intestinal) or external (through perianal skin)) results in a build-up of large numbers of larvae. Enormous numbers of these infective filariform larvae then penetrate the submucosa of the bowel wall and migrate, becoming widely disseminated throughout the body, in organs including the liver, pancreas, kidney, brain, and endocardium. Secondary Gram-negative polybacterial septicaemia, fluid depletion, massive alveolar haemorrhage, and disseminated intravascular coagulation may develop: a mortality rate of 86 per cent has been recorded.

This parasite is more common in temperate than in tropical and sub-tropical countries. Since it occurs in family or group members, group therapy may be indicated. The ova may be disseminated in dust. Autoinfection commonly occurs by direct transfer of ova from the perianal region to the mouth via the fingers. Retroinfection may also occur: ova which hatch on the perianal skin release larvae that crawl back into the colon, and occasionally into the vulva and genital tract.

Heavy infection causes haemorrhagic colitis. Tenesmus, proctitis, and recurrent straining lead to rectal prolapse, which is usually reversible following drug therapy. Trichuris dysentery syndrome has been associated with anaemia and growth retardation which is reversed after effective drug treatment.

A direct diagnosis of the intestinal nematode infection is usually made by finding the ova or larvae in stools using standard laboratory methods of examination. The Kato and Muira thick smear stool technique is recommended for the detection of light infections with Ascaris or Trichuris; the Baermann funnel filter technique is used to detect larvae in the stool of patients with strongyloidiasis. The adult worm may also be directly identified.

Nematode infections can also be diagnosed indirectly using immunological and biochemical tests such as haemagglutination, indirect immunofluorescence, radioimmunoassay, enzyme-linked immunosorbent assay, or immunoblot techniques. Most of these are not practical in the current clinical situation because of cross-reactivity and the problem of mixed infections. However, immunofluorescent and enzyme-linked immunosorbent assays may be useful in patients with chronic strongyloidiasis, in whom demonstration of the larvae may be difficult.

Many safe and effective drugs are now available; some are effective as single-dose therapy and are therefore useful for mass treatment; some have a broad spectrum of action and are particularly useful in patients infected with multiple parasites.

Bar-Maor JA, De Carvalho JLAF, Chappell J. Gastrograffin treatment of intestinal obstruction due to Ascaris lumbricoides. J Pediatr Surg 1984; 19: 174 - 6.

Brophy PM, Pritchard DI. Immunity to helminths. Ready to tip the biochemical balance? Parasitol Today 1992; 8: 419 - 22.

Cooper ES, Whyte-Alleng CAM, Finzi-Smith JS, MacDonald TT. Intestinal nematode infections in children: the pathophysiological price paid. Parasitology 1992; 104: s91-s103.

Khuroo MS, Zargar SA, Mahajan R. Hepatobiliary and pancreatic ascariasis in India. Lancet 1990; 335: 1503 - 6.

Kingston IB. Nematode collagen genes. Parasitol Today 1991; 7: 11 - 15.

Louw JH. Abdominal complications of Ascaris lumbricoides infestation in children. Br J Surg 1966; 53: 510 - 21.

Maddern GJ, Denison AR, Blumgart LH. Fatal Ascaris pancreatitis: an uncommon problem in the West. Gut 1992; 33: 402 - 3.

Martzen MR, McCullen BA, Smith NE, Fujikawa K, Peanasky RJ. Primary structure of the major pepsin inhibitor from the intestinal parasitic nematode Ascaris suum. Biochemistry 1990; 29: 7366 - 72.

Ochoa B. Surgical complications of ascariasis. World J Surg 1991; 15: 222 - 7.

Pawlowski ZS. Ascariasis. In: KS Warren, AAF Mahmoud, eds. Tropical and Geographical Medicine, 2nd edn. New York: McGraw Hill 1990: 369 - 78.

Pawlowski ZS, Schad GA, Stott GJ. Hookworm Infections and Anaemia. Geneva: WHO 1991: 1 - 96.

Pinus J. Surgical complications of Ascaris. Progr Pediatr Surg 1982; 15: 79 - 86.

Schulman A. Non-western pattern of biliary stones and the role of ascariasis. Radiology 1987; 162: 425 - 30.

Sher A, Coffman RL. Regulation of immunity to parasites by T cells and T cell-derived cytokines. Ann Rev Immunol 1992; 10: 385 - 409.

Surendran N, Paulose MO. Intestinal complications of roundworms in children. J Pediatr Surg 1988; 23: 931 - 5.

Vince J. Helminthiasis. In: P Stanfield, M Brueton, M Chan, M Parkin, J Waterston, eds. Diseases of Children in the Subtropics and Tropics, 4th edn. London: Edward Arnold 1991: 633 - 48.