Visceral Larva Migrans and Other Uncommon Helminth Infections


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Visceral Larva Migrans and Other Uncommon Helminth Infections



Theodore E. Nash *



Most helminths that infect humans are relatively host specific to humans, undergo characteristic migration and development, and are found in typical anatomic locations. However, these helminths sometimes undergo atypical or aborted migrations and cause symptoms or signs because of their unusual or ectopic location. A good example of this is the deposition of schistosomal ova and the subsequent granulomatous inflammatory lesions in the spinal cord or brain. In addition, some helminths of animals can also infect humans. Examples are Echinococcus granulosus and Trichinella spiralis, which commonly infect humans, migrate and develop normally, and reside in locations similar to those in the animal host. In contrast, other helminths of animals are unable to develop or migrate normally. Commonly, they undergo prolonged aberrant migrations or locate abnormally in the tissues as underdeveloped larvae and incite an eosinophilic inflammation that is responsible for many of the symptoms and signs of these infections. Although a large number of animal parasites may infect humans, most do so rarely. In contrast, some helminths of animals infect humans more commonly and cause distinctive clinical syndromes (Table 292-1), sometimes associated with characteristic epidemiology, exposure history, and geographic locations. More often than not, similar clinical syndromes are caused by a group of related parasites. The diagnosis is suggested on clinical and epidemiologic grounds. Although pathologic examination of tissue can sometimes establish the diagnosis, the detection of larvae is commonly unrewarding. Serologic tests are sometimes helpful (see “Visceral Larva Migrans [Toxocariasis]”) but usually are not fully evaluated, are experimental, or are unavailable.



The diagnostic procedures used to detect infections differ for each parasite, so a clear idea of the potential causes is essential. The physician must understand the sensitivity of the diagnostic procedures and the abilities of the laboratory personnel performing them.



Visceral Larva Migrans (Toxocariasis)


Visceral larva migrans (VLM) is a syndrome characterized in its most florid state by eosinophilia, fever, and hepatomegaly. It is caused primarily by infection with Toxocara canis but also, less frequently, by Toxocara cati and other helminths.13



Life Cycle in the Dog


Toxocara canis infects dogs and related mammals by a number of mechanisms.1 Most commonly, ingested eggs hatch in the small intestine, and the resulting larvae migrate to the liver, lung, and eventually in the mucus layer of trachea. They are then swallowed and mature in the lumen of the small intestine, where eggs are shed. Other larvae migrate to and remain dormant in the muscles but are capable of development even years after the primary infection, particularly in pregnant bitches. During pregnancy, larvae again develop and infect the puppies transplacentally and transmammarily. Not uncommonly, infective larvae are found in the feces of the puppies. Eggs are not infectious when passed in the feces and take 3 to 4 weeks to develop. They are hardy and often remain viable for months. Large numbers of viable eggs contaminate the environment because of the high prevalence of infection in dogs and the ability of eggs to survive relatively harsh environmental conditions. Humans become infected mostly from ingesting viable ova that contaminate the soil where dogs defecate. Ingestion of raw organs containing larvae, which is common in some regions, is another means of infection.4



Infection in Humans


Prevalence


Toxocariasis is prevalent wherever dogs or cats are found, and Toxocara eggs are able to survive. The prevalence of infection or disease in humans is not known, but seroepidemiologic studies show wide differences in prevalence, depending on the population tested. In the United States, seropositivity ranged from 2.8% in an unselected population,5 to 23.1% in a kindergarten population in the southern United States,6 to 54% in a selected rural community.7 None of the seropositive persons had recognizable disease.



Clinical Manifestations


Visceral larva migrans occurs most commonly in children younger than 6 years, frequently after ingestion of contaminated soil.3,5 Disease manifestations vary and range from asymptomatic infection to fulminant disease and death, but it is increasingly appreciated that most infections are asymptomatic. Those who come to medical attention most commonly complain of cough, fever, wheezing, and other generalized symptoms.68 The liver is the organ most frequently involved, and hepatomegaly is a common finding, although almost any organ can be affected. Splenomegaly occurs in a small number of patients, and lymphadenopathy has been noted. Lung involvement with radiologic findings has been documented in 32% to 44% of patients, but respiratory distress occurs rarely. Skin lesions, such as urticaria and nodules, have also been described. Seizures have been noted to occur with increased frequency in VLM, but severe neurologic involvement is infrequent.9 Eye involvement in VLM is unusual but has been documented (see “Ocular Larva Migrans”). Eosinophilia, usually accompanied by leukocytosis, is the hallmark of VLM. Laboratory findings include hypergammaglobulinemia and elevated isohemagglutinin titers to A and B blood group antigens, which are caused by the host’s immune response to cross-reacting antigens on the surface of T. canis or T. cati larvae. Serologically positive populations may be at increased risk for seizures.10



Diagnosis


The diagnosis of VLM is usually suggested clinically by the presence of eosinophilia, leukocytosis, or both in a young child also presenting with hepatomegaly or signs and symptoms of other organ involvement. A history of pica and exposure to puppies is common. In the United States, patients are more commonly black and from rural areas.


The diagnosis is definitively confirmed by finding larvae in the affected tissues by histologic examination or by digestion of tissue; however, larvae are frequently not found. Computed tomography (CT) scans have demonstrated ill-defined hypodense round lesions in the liver of patients with VLM, the basis of which is not clear.4 An enzyme-linked immunosorbent assay (ELISA), using extracts of excretory or secretory products of T. canis larvae, appears specific and useful for confirming the clinical diagnosis.11 However, recent studies suggest that Western blotting of excretory-secretory antigens are more specific and sensitive.12 Toxocara antibody titers in populations without clinically apparent VLM vary dramatically, and elevated titers cannot definitively establish the diagnosis.



Differential Diagnosis


Eosinophilia, fever, and hepatomegaly are frequently caused by helminths that migrate through the body. Baylisascaris procyonis (an ascarid of raccoons) is a recognized cause of larval migrans in the United States.13 Others are acute schistosomiasis, Fasciola hepatica infections, Ascaris lumbricoides abscess of the liver, acute liver fluke infections (Clonorchis sinensis, Opisthorchis viverrini), complications from Echinococcus infection of the liver, Capillaria hepatica, and other invasive helminths. Diseases not caused by parasitic infections should also be considered. Children with mild disease may manifest only eosinophilia.



Treatment and Management


Most patients recover without specific therapy. Treatment with anti-inflammatory or anthelmintic drugs may be considered for those with severe complications usually caused by involvement of the brain, lungs, or heart. There is no proven effective therapy, although albendazole, mebendazole, diethylcarbamazine, and other anthelmintics have been used. Indeed, injury to the parasite may provoke an intense inflammatory response, leading to worsening of the clinical picture. Corticosteroids have been used with and without specific antilarval therapy, with some reports of improvement.



Prevention


Visceral larva migrans can be easily prevented by a number of simple but effective measures that prevent T. canis or T. cati eggs from contaminating the environment and children from ingesting eggs. Dogs, particularly puppies, should be periodically tested and treated for Toxocara and other worms. Pica should be prevented. To prevent defecation by dogs and cats in sandboxes where young children play, they should be covered when not in use.



Ocular Larva Migrans


Ocular larva migrans is caused primarily by an infection of the eye with T. canis larvae.14,15 Although a present or past history of clinically recognized VLM has occasionally been noted, almost all patients present with unilateral eye visual loss without a past history or present systemic symptoms or signs. Presumably, a larva becomes entrapped in the eye by chance, resulting in an eosinophilic inflammatory mass. Children are most commonly affected and, on the average, are older (mean, 8.6 years in one study) than those diagnosed with VLM. Although the most common lesion is a chorioretinal granuloma in the posterior pole or occasionally more peripherally, diffuse panuveitis may also be seen. Retinal detachment may occur. This entity was first recognized in the examination of eyes enucleated for the treatment of presumed retinoblastoma, and it remains the most important distinction that ophthalmologists must make in children with subretinal lesions.14


Eosinophilia, hepatomegaly, and other signs and symptoms of VLM are usually lacking. The diagnosis is established clinically. Although the serum titers to Toxocara larvae are higher than those of a control population,16 many patients with ocular larva migrans have low or negative titers. However, elevated vitreous17 and aqueous fluid titers18 to Toxocara larvae, compared with serum levels, appear useful for establishing the diagnosis. There is no specific therapy.


A characteristic clinically recognizable syndrome, diffuse unilateral subacute neuroretinitis is caused by infection with helminth larvae of B. procyonis and Toxocara spp.19 and other unidentified nematodes.20,21 A motile larva is commonly found in or below the retina. Photocoagulation is curative. Anthelmintic therapy such as albendazole may be effective.



Baylisascariasis


Baylisascaris procyonis, an ascarid of raccoons, is a recognized cause of visceral larval migrans in humans and many other animals.2224 The life cycle is similar to that of dog and cat ascarids, and infection occurs after ingestion of ova excreted in raccoon feces that subsequently contaminate soil and the environment. Although the clinical manifestations are similar to those caused by dog and cat ascarids, severe and commonly fatal eosinophilic meningoencephalitis occurs in more than half the cases. Eye involvement is common and is one of the known causes of diffuse unilateral subacute neuroretinitis.19,20 The diagnosis is established by detecting typical larvae in tissues; an experimental serologic examination is useful.25 There is no proven therapy. Of the available drugs, albendazole and corticosteroids are most commonly tried.20



Anisakiasis


Anisakiasis is caused by the accidental infection of humans by larvae found in saltwater fish and squid. The definitive hosts are marine mammals. The clinical syndrome is caused by penetration of larvae into the stomach or small intestine. It is characterized by upper or lower abdominal symptoms, or both. The diagnosis is suggested by a history of ingesting raw, salted, pickled, smoked, or poorly cooked fish.26



Life Cycle in Marine Mammals


Larvae of the family Anisakidae, including Anisakis, Pseudoterranova, and occasionally other genera, can accidentally infect humans.1,2729 The adults are found in the stomach of marine mammals. The eggs, passed in the feces, hatch as free-swimming larvae, are ingested by certain crustaceans, and are eaten by fish and squid. When ingested by appropriate marine mammals, such as dolphins, seals, and whales, the larvae burrow head first into the stomach. When consumed by humans, the larvae attempt, many times successfully, to burrow into the stomach or intestine, resulting in typical symptoms.



Clinical Syndrome


Anisakiasis occurs after ingestion of raw or improperly cooked marine fish. The disease, initially recognized in the Netherlands after the ingestion of raw herring, is most frequently reported from Japan, where raw fish is commonly eaten. In the United States, infection is still uncommon but is now more frequently recognized because of increased ingestion of raw fish, particularly Pacific salmon. Cod, halibut, pollock, greenling, herring, anchovies, hake, tuna, sardines, and mackerel are other fish that have been implicated.


Clinical manifestations are caused by penetration of worms into the gastrointestinal tract, usually the stomach but also the lower small intestine, most commonly the ileum.2830 On occasion, throat irritation is followed by coughing up the characteristic worm. Initial invasion is associated with acute symptoms, whereas the presence of worms for longer periods causes chronic symptoms. The symptoms and the location of the worms depend somewhat on the genus, with Pseudo­terranova commonly associated with infection of the stomach and Anisakis with the intestine. Symptoms usually occur within 48 hours after ingestion, but this pattern is variable. With gastric anisakiasis, patients complain of intense abdominal pain, nausea, and vomiting. Small intestinal involvement is less common and results in lower abdominal pain and signs of obstruction mimicking those of appendicitis. The incubation period is shorter with gastric involvement, but small bowel infection commonly causes eosinophila.31 Symptoms may be chronic, sometimes lasting for months and, rarely, years. These symptoms are associated with intestinal masses containing the parasite and are sometimes confused with a tumor, regional enteritis, or diverticulitis. Worms are occasionally located ectopically outside the gastrointestinal tract. Anisakis larvae in seafood have been implicated as a cause of acute allergic manifestations, such as urticaria, pruritus, angioedema, and anaphylaxis, with or without accompanying abdominal gastrointestinal symptoms in patients who ingest raw fish.3236 In vitro studies and skin tests indicate that sensitization to Anisakis antigen is common in this population, whereas sensitization to fish is uncommon.29,3436



Laboratory Findings


Eosinophilia is usually absent in patients with gastric or intestinal anisakiasis31 but is usually present in small bowel involvement. Leukocytosis is not consistently present with acute anisakiasis but has been noted in almost two thirds of the patients with intestinal involvement in one series.



Diagnosis


Anisakiasis should be considered in anyone with a history of ingesting raw marine fish and suggestive abdominal symptoms. A definitive diagnosis can be established by endoscopy, radiographic studies, or pathologic examination of tissue. In the upper gastrointestinal tract, worms are found partially embedded in any area of the stomach and may be associated with localized mucosal edema, erosions, or mass lesions.37,38 Upper gastrointestinal radiographic studies may reveal the outline of a worm associated with mucosal edema or tumor formation. Removing the worm during endoscopy definitively establishes the diagnosis and is curative.30 Intestinal anisakiasis is diagnosed clinically. Varied degrees of thickening of the walls and narrowing of the lumen of the ileum or jejunum are found on radiographic studies. High-resolution ultrasonography has demonstrated small intestinal wall thickening and localized ascites around the involved section of bowel. Examination of aspirated ascites has revealed a preponderance of eosinophils.39 Lesions resolve within 2 to 3 weeks. On occasion, removal of the intestinal mass is required to establish the diagnosis and effectively treat the patient. Tissues show inflammatory masses, many eosinophils, and the characteristic helminth. Serologic tests are not generally available but may be useful, particularly in patients whose symptoms have lasted longer than 1 week.40

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Jul 1, 2017 | Posted by in INFECTIOUS DISEASE | Comments Off on Visceral Larva Migrans and Other Uncommon Helminth Infections

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