Ascaris lumbricoides (Ascariasis)
Authors: Ore Samuel Asaolu, Ph.D., OIfeanyi Emmanuel Ofoezie, Ph.D., Ogbonna Cyprian Onyeji, Ph.D.
Parasitology
Ascaris lumbricoides is one of the commonest and most prevalent parasites infecting humans in the world today (14,42). Ascariasis is endemic in parts of tropical and temperate regions of the world, where there is sufficient moisture and particularly in areas characterised with poverty, ignorance and low standard of hygiene and sanitation(20). Over one billion people are infected world-wide (4), most of whom reside in developing countries of Africa, Asia and South America (3,25).
Ascaris lumbricoides is the largest nematode inhabiting the human alimentary tract, usually found residing in the jejunum of the small intestine (3,4,16). The males are usually smaller than the females and have a curved posterior end. They measure 15 to 31 cm in length and 2 to 4 mm in width while females are 20 to 49cm long and 3 to 6 mm wide. Life worms appear creamy white to yellow and often translucent with a pinkish tint. A. lumbricoides has a direct life cycle. Eggs released by the females are passed with host faeces. The eggs appear brownish in colour. Both fertilised and unfertilised eggs can be detected in host faeces. Fertilised eggs are round to oval, measuring 45 to 75 by 35 to 50 μm, containing a developing embryo and covered by a thick shell with an outer surface that appears rough or irregular. The unfertilised eggs are larger and elongated in shape, measuring 60 to 100 by 40 to 60 μm.
The detailed life cycle of A. lumbricoides has been described previously (16). Under conducive climatic conditions of temperature (25-30°C), high humidity and sufficient supply of oxygen, fertilised eggs moult once and embryonate in 15 to 35 days to become infective. The infective egg contains a second stage larva, coiled within the eggshell. Infection occurs when the infective eggs are ingested with contaminated food and water. The eggs hatch into larvae in the jejunum a few hours after being swallowed. The larvae penetrate the intestinal mucosa, migrate via the portal vessels and lymphatic system into the liver from where they are carried through the heart into the lungs. Subsequently, they penetrate the capillary walls and enter into the lung alveoli. After about 10 days in the lungs they move up the bronchi and trachea to the pharynx and are then swallowed down the oesophagus. This migratory phase lasts for about two weeks during which the larvae undergo two additional moults. On arrival at the small intestine, the fourth moult occurs and the larvae form immature adult worms. The worms mature and copulation takes place between adult male and female worms. The release of eggs by the female worm commences about 60 days after swallowing an infective egg. Adult worms survive for one to two years in the human host during which time each female worm produces about 200,000 eggs per day. Diagnosis is by examining the host faeces for Ascaris eggs or adult worms. The fertilised egg of A. lumbricoides is the most resistant of all soil-transmitted helminth eggs and can remain viable in the environment for many years.
Epidemiology
In many endemic communities, people are exposed to infection from birth and are continually at risk from re-infection because of poor sanitation, low standard of personal hygiene and constant exposure to enormous numbers of A. lumbricoides eggs discharged into the environment by the female worms (26). In many communities, prevalence may be in excess of 80% (4,14). Age related distribution shows that prevalence reaches a peak between the ages of 4 and 14 years. Intensity of infection measured by worm burden after expulsion chemotherapy or by egg excretion per gram of host faeces indicates that children harbour more worms than adults in any given community.
It has also been observed that the distribution of worms in a human population is over dispersed, such that the majority of individuals in a community carry few or no worms while a few individuals carry most of the worms in the community. Consequently, young children and individuals disposed to heavy worm burden are targets for attention when chemotherapy is used for control and for reduction of morbidity.
Clinical Manifestations
Several Ascaris larvae migrating from the intestine to the other organs are destroyed in the liver and lungs. The remains of the disintegrating larvae induce most of the eosinophilia seen in ascariasis. Pulmonary manifestation is the usual symptom. This presents as a slight cough for a few days or, in areas where transmission is seasonal, as a severe seasonal Loffler's pneumonia-like syndrome (4, 22).
Adult worms residing in the intestine may induce mild occasional abdominal pains. When the worm load is heavy, and especially in children, the abdominal pain is severe and the patient may be restless with loss of appetite, occasional vomiting and intermittent loose stools, constipation, passing of worms from the rectum or the mouth, colicky, abdominal distension and abnormal abdominal sounds.
Laboratory Diagnosis
Each female worm produces a daily output of 200,000 ova and hence direct smear examination of the stool is sufficient for diagnosis of ascariasis. The fertile ovum is broadly oval, has a thick shell with an outer, course, mammillated albuminous covering, and measures 45 to 75μm in length by 35 to 50 μm in breadth.
Pathogenesis
The pathogenesis of ascariasis is generally related to organ damage and host reactions to larval migration as well as the number and location of adult worm in the body. Ascaris larvae migrating through the intestinal mucosa, liver and lungs provoke hypersensitivity reaction in the human host. Some of the larvae may be immobilised and covered with eosinophils, resulting in the formation of granulomas. In the lungs, movement of the larvae from the blood vessels into the air spaces results in haemorrhage. There is oedema of the alveoli. Alveolar sacs are filled with a serous exudate, the peribronchial tissues becoming infiltrated with eosinophils and neutrophils, and mucus production in the bronchi is increased. Known as Loeffler's syndrome, it gives rise to dry cough, high fever and bronchial asthma. The effect is severe when the number of larvae is large or when transmission is seasonal.
The presence of adult A. lumbricoides in the intestine induces disordered changes in the jejunal mucosa and intestinal muscle layers. There is a coarsening of mucosal folds, shortening of the crypt depth, reduced mucus production and hypertrophy of the intestinal muscle layers (32, 52). Protein energy malnutrition, reduced food intake and impaired cognitive function in children are associated with these problems of ascariasis (23).
Due to its large size and aggregating and migratory activities, adult Ascaris frequently precipitates severe complications. Fever, ingestion of some drugs or food by the host, and surgical anaesthesia have been suggested as predisposing factors for worm migration from their usual location (3). Worms may move toward the upper gastrointestinal tract and become vomited (55). In heavy infections, several worms may ball up and cause intestinal obstruction (8, 51, 55). This may be accompanied by such complications as intussusceptions, volvulus, haemorrhagic infarction and perforation of the intestine. Invasion of the biliary duct, hepatic abscesses, acute pancreatitis, acute appendicitis, peritonitis and obstruction of the upper respiratory tract are also reported (3, 6, 40, 51, 55, 57). Allergic reactions such as asthma, eosinophilia and urticaria have been reported in laboratory workers who have had previous exposure to materials from Ascaris worms (4, 54).
SUSCEPTIBILITY IN VITRO AND IN VIVO
Ascaris lumbricoides is regarded to be host-specific to humans although there are reports of mature worm infections in a variety of other mammals. Although A. lumbricoides and A.suum (an ascarid of pigs) are regarded as separate species, the two worms resemble each other closely biologically. The life cycle of A. suum including its migrating cycle_in pigs from the intestine through the liver, lungs, trachea and back to the intestine is very similar to that of A. lumbricoides . Due to its ease of availability and convenience in carrying out experimental infections and the need to develop anthelmintic drugs, a considerable amount of biochemical research has been conducted on A. suum in pigs. Hence much of our knowledge on the biology, immunological and pathophysiological effects of A. lumbricoides in humans is derived from the results of laboratory investigations of A. suum in pigs and other laboratory animals such as guinea pigs, mice, rats and rabbits (15, 36).
ANTIMICROBIAL THERAPY
General
There are several drug formulations available for the treatment of ascariasis (Table 1). Levamisole, the drug of choice, is highly effective and well tolerated. It acts on the worm's nerve ganglia paralysing the musculature within minutes of contact resulting in the immediate ejection of the worms by normal peristaltic movement in less than 24 hours. Levamisole is available as 40 mg levamisole tablets and 40 mg/5 ml drinkable suspensions. The tablets are administered in a single dose of 1, 2 and 3 tablets for children below the age of 5 years, children and young adults between 6 and 16 years and adults 16 years and above, respectively (17, 28, 52).
Mebendazole, a benzimidazole derivative, interferes with the cellular tubulin formation in worms, disturbs glucose uptake and the normal digestive functions leading to instant autolytic process and death. The worms are expelled within 24 hours of drug administration, sometimes by mouth. Mebendazole is available as oral tablets, each containing 100 mg mebendazole and drinkable suspension containing 20mg mebendazole/ml. Both the tablet and the suspension are given in 6-regimens of 1 tablet (adults) or 5ml suspension (children below the age of 5 years) twice daily (morning and evening) for 3 consecutive days. An alternative dose of 500 mg single dose has also been found to be equally effective (1, 2, 23). However, mebendazole is not recommended for children below the age of two years. The drug is well tolerated having only mild and transient side effects. However, it is contraindicated in persons who have shown hypersensitivity to the drug and in pregnant women, although in the case of the later, the risk of prescription should be weighed against expected health benefits, since there is no proven embryo toxic or teratogenic activity in humans (40).
Albendazole, also a benzimidazole carbamate, is available in tablets of 200 mg albendazole and drinkable suspension of 20 mg albendazole/ml. It is administered in a single dose of 400 mg (2 tablets or 20 ml) to both adults and children above the age of 2 years.
Pyrantel, a tetrahydropyrimidine, is used in a single dose of between 5-10mg\kg body weight to a maximum of 1g. It acts by blocking the neuromuscular system of the worm, which becomes instantly immobilised and expelled. It is well tolerated. The good tolerance and lack of teratogenicity are advantages favouring the use of this drug in large scale mass chemotherapy programmes.
Piperazine also acts on the neuromuscular system of Ascaris causing a flaccid paralysis that results in the expulsion of the worm by peristalsis. It is generally well tolerated when taken in a single dose of 75mg\kg body weight to a maximum individual dose of 4g for adults and 2g for children (40). Piperazine is a less preferred drug for the treatment of ascariasis because of sporadic hypersensitivity and neurotoxic reactions associated with its administration. It is also associated with diplopia, myaclonus and renal dysfunction especially, in the elderly.
Nitazoxanide, a nitrothiazole benzamide has been reported to be effective against a broad range of parasites including Ascaris and other nematodes. The drug is administered at a dose of 1 tablet (500 mg) twice daily for 7 consecutive days. At this dose, it is very effective among all age groups (18).
Special Situations
Unusual Sites
The presence of Ascaris worms in unusual sites (i.e. sites other than the jejunum of the small intestine) arises when migrating larvae end up in ectopic sites, when adult worms wander into small orifices including the bile duct, the hepatic duct branches, the parenchyma or the pancreas, and when through perforated lumen, made by the worms or resulting from other infections (e.g. typhoid fever), the worms escape into the peritoneal cavity, retro peritoneum or the mediastinum (11, 30, 44, 57).
Pathological consequences of ascariasis of unusual sites could be very serious. Most frequently encountered conditions include ascaridic pyogenic cholangitis, empyema and perforation of the gall bladder, biliary calculi, granulomatosis, hepatic abscess and a host of other complications (3, 19, 29, 50). Options for the management of complications in ascariasis vary widely and depend on the type and severity of complication, the organ involved and the clinical state of the patients (3, 41).
Generally, it is advisable to approach all sub-acute cases with conservative medical treatment using one of the potent anthelmintic drugs. For acute cases, especially those involving rectorrhagia, toxicity and plain abdominal films with several air-fluid levels, surgical intervention appears the best option. Detailed description of the various surgical procedures have been described by several workers (3, 12, 34, 39,41, 43, 48, 55).
Immunosuppressed Hosts
There is a consistent indication that ascariasis is a non-opportunistic enteric infection in HIV-positive and AIDS patients (13, 45, 49, 50). Actually, there is a greater tendency for Ascaristo infect HIV-negative individuals than HIV-positive and enteropathic AIDS patients (35). The prevalence of ascariasis is also higher among HIV-positive patients without chronic diarrhoea than their counterparts with chronic diarrhoea suggesting that the infection is not a cause of diarrhoea which is a leading cause of morbidity and mortality among AIDS patients (10, 24, 53). Besides, there is no evidence that intensity and severity of ascariasis are higher among HIV-positive and AIDS patients than their uninfected counterparts suggesting that the immunocompromised status in HIV-positive and AIDS patients does not adversely affect ascariasis. Treatment of ascariasis among HIV and AIDS patients should therefore follow the normal procedure using the common anthelmintic drugs described in the preceding section. However, the immunocompromised status of the HIV positive and AIDS patients should be taken into consideration in treating complicated cases especially those involving the unusual sites.
Herbal Therapy
Most available alternative therapy is derived from plants. Plant-based anthelmintics are gradually gaining wider acceptance in China where they now serve as important alternative to the treatment of complications especially biliary ascariasis (57). The major ingredients for the formulation of traditional Chinese medicine (TCM) are derived from plants such as Prunus mume, Asarum heterotropoides,Zingiber officinale, Coptis chinensis, Angelica sinensis, Phellodendron amurense, Cinnamomum cassia, Panax qinseng and Zanthoxylum bongeanum (33,37,57,58). In Madagascar, the only African country with records of traditional herb treatment of ascariasis, four local herbs found to be very effective are Physcalis pernviana, Melia azedaracia, Chenopodium ambrosioides, Psiadia salviaefolia (31).
The traditional herbs could be taken singly or in combination with the more recent orthodox anthelmintic drugs. In a recent study, the efficacy of only TCM was compared with a combination of TCM and some orthodox drugs. Results revealed that both therapies were equally effective but the combination therapy has a slight advantage because it is associated with reduced episodes of vomiting thus reducing electrolyte imbalance and risk of dehydration (57).
ENDPOINTS FOR MONITORING THERAPY
Therapeutic endpoints are monitored using various diagnostic techniques, including laboratory, clinical and radiographic methods. The laboratory methods seek to identify and quantify adult worms, larvae and/or eggs of Ascaris lumbricoides before and after therapy to determine the progress and efficacy of the treatment (40). The most commonly used laboratory techniques for identifying and quantifying eggs in host faeces are the formol-ether concentration method and the Kato thin and thick smear (21). Adult of Ascaris worms expelled from the anus or the mouth could be identified using the classical characteristics of the worm as described in Section 1A. The larval stages are often seen exclusively in the sputum or the gastric washings. Although identification of these has been used in exceptional cases, it is neither common nor very sensitive and should therefore not be relied upon (40).
The clinical methods rely on the various signs and symptoms of ascariasis, not only to determine the stage of infection but also to monitor therapeutic effects. The importance of signs and symptoms is based on the fact that they increase in intensity and severity as infection progresses and resolve gradually with cure. Monitoring the direction and progress of clinical signs and symptoms is therefore a very reliable endpoint for determining therapeutic effect. The most important signs and symptoms used in clinical diagnosis of ascariasis include epigastric and right hypochondrium pain, vague abdominal pain (localised around the navel in children and mimics peptic ulcer or colicky pain around the epigastria in adults), fever, spontaneous expulsion of adult worms from the anus or mouth and presence of characteristic Ascaris eggs in stool (22, 44).
The radiological methods are limited to the X-ray of the chest or the abdomen. In chest X-ray, complications due to ascariasis may present as discrete soft bilateral densities that sometimes become confluent in the perihilar areas (22). In plain abdominal X-ray, roundworms appear as "whirlpool" pattern or as a longitudinal or transverse unit but these disappear following successful expulsion chemotherapy (55).
VACCINES
Although several efforts have been made at developing vaccines for effective prophylaxis of helmintic infections including ascariasis, none has proved effective enough to be commercially available.
PREVENTION
Prophylaxis of A. lumbricoides, can be effected by the application of various strategies including anthelmintic agents, treatment of excreta with ovicides, sanitation (safe disposal of excreta) and treatment of food before eating to remove and destroy Ascaris eggs. The prophylaxis of Ascaris by the use of anthelmintics is approached by three ways: mass chemotherapy, group-targeted chemotherapy, and treatment of individual cases.
Mass Chemotherapy
Mass treatment consists of treatment of all members of a given population at risk without a laboratory diagnosis. It has been asserted that mass treatment is more economical than treatment after diagnosis because the cost of technical skill and equipment for diagnostic procedure is saved. This method of control of ascariasis has been reported as the most effective and has been used with satisfactory results in several places (2, 27).
Group-targeted Chemotherapy
This involves chemotherapy targeted at specific groups of the population who are at highest risk of morbidity due to intestinal helminths. This group usually comprises pre-school and school-aged children, except in areas of extreme endemicity where all ages are uniformly infected (1, 56). It has been established that, in targeted chemotherapy the untreated portion of the population benefits from the drastic reduction in community egg load and subsequent fall in overall risk of infection (5, 9). This is attributable to an overall reduction in contamination of the environment with a resultant decrease in exposure of the whole community members to the infective stages of the parasite. For example, following periodic chemotherapy targeted at school children in Pemba, Tanzania, Ascaris infection was found to decrease significantly in all age groups (1).
Treatment of Individual Cases
In endemic areas without an organised control programme, individuals may take anthelmintic drugs periodically to prevent infection. Identification and treatment of these individuals is carried out mainly at the hospital level when such persons present with symptomatic complaints. This approach is most useful for identifying and treating individuals predisposed to infection with heavy worm burden in a community because it is only severe symptomatic manifestations often associated with very heavy infections that encourage individuals to go to hospitals (26). Hospital based individual treatments have therefore been suggested as a possible approach to reducing morbidity due to ascariasis in a community (5).
Drugs, Doses and Dosing Schedules
The same drugs are used for mass chemoprophylaxis as well as treatment and prophylaxis of individual cases. Many anthelmintics are highly effective for control of ascariasis and have been compared in many field trials (2, 56). The common drugs described for the treatment of Ascaris are also used for prophylaxis (see Section III). Levamisole (at a single dose of 2.5mg/kg of body weight), pyrantel pamoate (at a single dose of 10mg/kg), and mebendazole (at a dose of 100mg twice daily for three days) are effective prophylaxis against ascariasis (1, 2, 23). However, for long term effective prophylaxis, the drugs must be given repeatedly at a frequency depending on the rate of infection in a given area. For example, treatment with mebendazole every 4 months in a highly endemic area has been shown to significantly reduce prevalence and intensity of Ascaris infections (1). Similarly, levamisole and pyrantel pamoate may prevent Ascaris reinfections for only about 4-6 months after treatment. In a study of children in slums and villages in Bangladesh (25), individuals treated for Ascaris with levamisole were reinfected within a 9-month period. The pattern of re-infections in endemic communities underscores the limitations of using only chemotherapy in the control of ascariasis. It is, therefore, suggested that the efficacy of chemotherapy may be enhanced by improved sanitation and water supply (4). However, in areas where transmission is less intense, the appropriate re-treatment interval might be longer than 6 months (5, 27).
ADJUNCTIVE THERAPY
Anthelmintic drugs are effective for the treatment and resolution of ascariasis. However, complications of an infection with the parasite can result as evident in its infestation of the biliary tract (biliary ascariasis) and obstruction of the intestinal tract. With such complications, treatment with anthelmintic agents alone is ineffective, necessitating the application of adjunctive therapy such as surgery and the use of agents that are not antiparasitic.
Non-Anthelmintic Drugs
In massive infestations and obstructive complications of ascariasis, a variety of agents have been used to facilitate a resolution of the infection. For example, in massive infestation, toxins excreted by the worms cause toxicity in patients and such patients require aggressive management with intravenous infusion of crystalloids (20ml/kg lactated Ringer's solution) in a rapid bolus until acceptable urine output is achieved (1ml/kg/hr). In some cases with poor perfusion, a dopamine drip (3-5 mg/kg/min) is necessary. Also, in massive infestations of the intestinal tract, pre-treatment with saline laxatives or racine oil before administration of anti-worm medications has been advocated.55 The rationale being that the anthelmintic agents whose mode of action is through inhibition of glucose uptake (e.g. mebendazole) cause initial worm excitation and often result in more complications as the worms thrash around. Pre-treatment with a laxative or agent with a cathartic effect (e.g. racine oil) facilitate worm expulsion, and reduces the prospect of complications. Gastrografin, a hyperosmolar and welting agent, is another adjunct used in the resolution of intestinal obstructions. Administration of the agent for a washout effect has been found effective in relieving subacute intestinal obstruction (7).
Helminthic infections including ascariasis and hookworm, produce an array of pulmonary diseases in humans. Larval pulmonary migration generally is asymptomatic. However, symptomatic pulmonary disease may occur due to the effects of larval tissue migration, airway reactivity or bronchospasm and infectious bacterial complications from parasitic migration. Symptomatic treatment may be necessary with bronchodilators and systemic steroids or antibiotics for bacterial complications (46). Thus, it has been established that intestinal helmintic infections can contribute to the clinical symptoms of asthma in an endemic situation. This, may occur not only via a direct response to the parasite during pulmonary passage, but also through non specific presentation of allergic reactivity to environmental allergens (38).
Surgery
In the management of intestinal obstruction caused by Ascaris lumbricoides, the following indications for surgery have been noted: rectorrhagia, toxicity, plain abdominal films with several air-filled herds, and no response to medical treatment (55). The differential diagnosis includes acute appendicitis because of the similarity of presenting signs and symptoms (47). In biliary ascariasis, the endoscope's retrograde cholangiography may be effective in diagnosis but extraction of the worms through the endoscopes is not possible if the infestation is massive and the patient is in a critical state (3). Thus, surgical treatment is the most efficient in biliary ascariasis particularly in cases with large number of worms, septicaemic and hepatic abscesses. The traditional Chinese medicine (TCM) described in Section IIB (3) has also proved very promising in the treatment of biliary ascariasis (57).
CONTROVERSIES, CAVEATS AND COMMENTS
Teratogenicity and embryotoxic effects have been produced by mebendazole in rodents but these effects were not observed in other experimental animals such as dogs, sheep and horses. However, there is a possibility that the risk of mebendazole teratogenicity in rodents may also occur in humans. Thus, it is recommended that the drug should be used with caution in pregnancy and in under aged children (<2 years old), although there is no direct clinical evidence to warrant the contraindication (17, 40).
The metabolism of mebendazole is inhibited by cimetidine, a drug used in the treatment of peptic ulcer. This drug-drug interaction results in elevated plasma levels of mebendazole if it is concurrently administered with cimetidine. Such increased plasma mebendazole concentration may be therapeutically beneficial in the treatment of helminth infections of sites other than the lumen of the gastrointestinal tract (e.g. the pulmonary stage ascariasis). On the other hand, mebendazole increases plasma levels of theophylline, hence, there may be need to reduce the dose of theophylline (a muscular relaxant used mainly as a diuretic) when combined administration of both drugs is indicated.
Levamisole is no longer available in some countries especially the developed countries of Europe and America. This may be due to the several cases of agranulocytosis recently observed to follow prolonged use of the drug. However, it is still the drug of choice for treatment and prophylaxis of ascariasis in endemic countries (1,5). It is, however, reported to have ammunomo properties, for which reason it is under clinical investigation for use in immunodeficiency diseases.
No teratogenicity has been reported for pyrantel and the drug also does not have any specific contraindications. The action of the drug, is however, antagonized by piperazine and the two should not be given together. The good tolerance of the drug may not be unconnected with the fact that it is poorly absorbed from the gut, suggesting very minimal systemic side effects. On the other hand, piperazine is well absorbed from the gut and the risk of side effects associated with its use includes neurotoxicity. It is also contraindicated in liver disease, renal impairment, convulsive disorders and pregnancy. It should not be given concurrently with pyrantel as they antagonize the action of each other.
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Tables
Table 1: Major Drugs Used in the Treatment of Ascariasis [Download PDF]
Drug formulation (manufacturer) | Common names | Activity | Doses (mg) | Half-life (hrs) | Side-effects | Active chemical | Date introduced | Remark |
---|---|---|---|---|---|---|---|---|
Levamisole (ICI; Janssen; Zeneca) | Ketrax, Decaris | Excellent | 40-150* single dose oral | 4 | Mild nausea & vomiting | Imidazothiazole | 1968 | Drug of choice |
Mebendazole (Janssen) | Vermox, Pentelmin | Very good | 100 2 ice daily for 3 days, oral | Transient abdominal pain & diarrhoea | Benzimidazole carbamate | 1971 | ||
Albendazole (Smith-Kline & French) | Zentel | Very good | 400 single dose, oral | Abdominal discomfort, headache | Benzimidazole carbamate | 1979 | ||
Pyrantel (Pfizer) | Combantrin | Very good | 5-10mg\kg to max. 19g single dose oral | Mild nausea, abdominal cramps, vomiting & diarrhoea | Trtrahydropyrimidine | 1966 | ||
Piperazine (Elixir & others) | Antezin (& others) | Good | 40 single oral | Diplopia, myoclonus and mild renal dysfunction in the elderly | Diethylenediamine |
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Loreille O, et al. Evolution of ascariasis in humans and pigs: a multi-disciplinary approach. Mem Inst Oswaldo Cruz 2003;98:39-46.