Aetiology: the biology of the parasite

Adult worms live in the pulmonary arteries of rats; larvae from hatched eggs ascend the airways, are swallowed, and so reach the faeces. Molluscs ingest these larvae, and after two moults they are infective when eaten by a rodent. In the rat, infective larval worms migrate to the cerebral grey matter, where they start to mature. They then move to the meninges and enter the venous sinuses, thereby reaching the pulmonary arteries, where maturation is completed. Infective larvae from a mollusc can also enter a second or third intermediate host, in which they undergo no further development until they enter a mammalian host. Such supernumerary hosts are termed paratenic hosts, and are important sources of infection in humans.

Development in humans reaches the immature adult stage, measuring 11 to 15 mm in length. Nearly all will die in the superficial cortex, brainstem, and meninges, causing vigorous tissue reactions; very few reach the lungs.

Epidemiology

The parasite is endemic and causes human outbreaks in South-East Asia, east Asia, Oceania, and the Caribbean. Sporadic cases are reported in many other countries, usually in travellers. Most recent outbreaks have been in mainland China, Taiwan, Thailand, and Japan. In the Pacific epidemics have occurred in Hawaii, Samoa, and the Solomon Islands. In the Carribbean most cases are reported from Cuba, Costa Rica, and Jamaica. All ages can be affected, and outbreaks have occurred after weddings and feasts; infections are often seasonal. The modes of transmission differ geographically, by age and social group, and with time.

The principal rodent hosts are Rattus rattus, R. norvegicus, R. alexandrinus, and R. exulans. The prevalence in rats in endemic areas may be 40% or more. The geographical spread and population increase of these peridomestic rodents has increased the zoonotic reservoir; wildlife is now infected in the southern United States of America. Another factor leading to the increase in human infection has been the dispersal by human agency of the edible giant African land snail Achatina fulica, from Madagascar in 1800, eastwards across the Indian Ocean and the Pacific, to reach Hawaii in 1936. The freshwater golden apple snail Pomacea canaliculata, which is highly susceptible to the parasite, was recently introduced into Asia, where it has colonized paddy fields and caused disease when served raw in restaurants in China, Taiwan, and Japan. The popularity of heliculture, the cultivation of exotic snails for food, and keeping them as pets, facilitates the spread of the parasite. Raw snails are eaten as a delicacy and for medicinal purposes; salads may contain small undetected molluscs, their slime trails, or planarians. An outbreak in Taiwan followed the drinking of raw vegetable juice. In Thailand, Pila spp. snails are a seasonal delicacy eaten by all the family, but only young men take them raw with alcohol.

Paratenic hosts include freshwater prawns, land and coconut crabs, frogs, and land planarians, which cause infection if eaten raw; drinking-water may contain tiny immature prawns, especially after heavy rains. In Thailand, the yellow tree monitor lizard is an important paratenic host. In the Ryukyu islands of Japan, patients are usually infected by eating raw snails or toad liver for medicinal purposes.

Pathology

Inflammatory granulomatous lesions, sometimes track-like, occur predominantly in the cortical grey matter and the meninges, but also in the brain stem and cerebellum; nerve roots and the spinal cord may also be affected. Live worms are occasionally found at autopsy, and dead worms are found in many lesions. The number of worms found varies greatly, and may reach several hundred; worm tracks in the tissue and meninges are surrounded by a cuff of eosinophils; Charcot–Leyden crystals derived from eosinophils are numerous. Rarely, adult worms have been found in human lung at autopsy. Ocular infection derives from worms that have migrated across the cribriform plate.

Clinical features

After an incubation period of 1 to 4 weeks the onset is acute, with headache (intermittent at first), together with nausea and vomiting. There is constitutional upset and frequently menigism; fever is unusual. The illness is often self limiting over a period of 4 weeks. Cranial nerve lesions are seen in the optic, abducens, and facial nerves. Less common are seizures, confusion, and radiculopathy (with paraesthesia, root pains, or weakness). Long-tract signs and impaired consciousness are uncommon, except in severe cases, but spinal cord damage can cause sphincter disturbance.

Ocular complications include retinitis, retinal haemorrhages, optic neuritis, and larval worms in the vitreous, anterior chamber, or beneath the conjunctiva (Fig. 7.9.6.1). Rarely, migration to the lungs produces clinical evidence of pneumonitis. Numerous eosinophils occur in the cerebrospinal fluid, and there is blood eosinophilia.

• View full-sized figure
• Download figure as PowerPoint slide

Fig. 7.9.6.1

Parastrongylus under the conjunctiva in a Thai girl with a left facial nerve palsy.

(Copyright D A Warrell.)

Diagnosis

Lumbar puncture reveals high opening pressure, with a clear or lightly turbid cerebrospinal fluid containing 500 to 2000 cells/mm³ (of which 10–>90% are eosinophils); protein levels are usually elevated, with normal or less commonly reduced glucose. Detailed examination at low power reveals larval or immature adult worms in up to 25% of cases, measuring 5 to 15 mm in length. Cerebrospinal fluid changes may persist for up to 3 months. CT or MRI may reveal focal cortical abnormalities. Serology using antigens from fourth-stage larvae is useful, but cross-reactions with other nematodes can cause difficulty. Commercial serological tests are not yet available. Techniques to detect worm antigens in cerebrospinal fluid and serum have also been developed.

Differential diagnosis is from other helminth infections affecting the nervous system, as eosinophils are otherwise rare in cerebrospinal fluid. A detailed geographical and dietary history is essential; conditions to be considered include gnathostomiasis, paragonimiasis, schistosomiasis, and neurocysticercosis. A particular problem in Thailand is confusion with Gnathostoma spinigerum, which more commonly causes long-tract signs, bloody or xanthochromic cerebrospinal fluid, neck stiffness, and clouding of consciousness.

Treatment, prognosis, and control

Although worm death might aggravate the clinical condition, clinical studies support the use of the anthelmintics albendazole or mebendazole together with prednisolone. However, in a recent prospective trial prednisolone alone was as effective as prednisolone plus albendazole. Prednisolone alone is now often the recommended treatment, although prednisolone plus albendazole is still used in China and probably elsewhere. Such treatment hastens recovery and relieves headache; it probably improves the prognosis in severe cases. Ocular disease may require laser therapy and larvae in the eye chambers should be removed surgically.

Mortality rates are generally low in uncomplicated cases and depend mainly on the number of infective larvae ingested; some patients develop encephalitis and pass into coma after about 2 weeks, and their prognosis is then very poor. Most patients improve in 2 to 4 weeks, but focal neurological deficits can persist for longer; partial relapse after 2 months of illness may represent a reaction to dying worms. Some cases are relatively mild and can be discharged within a few days; during epidemics, mild cases may need only outpatient care.

Control measures include health education to limit the ingestion of raw high-risk dietary items, and unwashed salads. Warnings may be necessary regarding raw molluscs, amphibians, and reptiles used for medicinal purposes. Rodents in vegetable gardens and the peridomestic environment should be controlled.

Aetiology: the biology of the parasite

In both the rodent and human hosts the worms are located in the ileocaecal mesenteric arteries. The cotton rat Sigmodon hispidus is the principal reservoir host, but other species of rodent (including the coatimundi) are also involved, and even dogs and marmosets. In the rodent hosts worm eggs embolize to gut-wall capillaries, and the hatched larvae pass into the gut lumen. Veronicellid slugs, especially Vaginulus plebeius, eat rodent faeces containing larvae, and these develop into infective larvae in the fibromuscular tissue of the mollusc after two moults over a period of 18 days. Infective larvae can persist in the slug for several months or be shed in slime trails. The prepatent period in rats eating infected slugs is 24 days.

In human infections the worms reach maturity, but the embryonated eggs do not hatch.

Epidemiology

Infections occur especially in Costa Rica, Nicaragua, Guatemala, and Honduras, but also sporadically elsewhere in the Americas from the United States of America to Argentina, and some Caribbean islands. Recently, infections have been increasingly recognized from southern Brazil. Small veronicellid slugs and their slime trails are the source of infection in man; infection rates in these hosts can reach 85%. Small or chopped slugs may be unnoticed on fallen fruits or in salads; their mucus also contains infective larvae. Many cases are in schoolchildren, but infants and older persons are also affected. Seropositivity in endemic areas suggests that there are unrecognized infections.

Pathology and clinical features

Lesions primarily affect the small arteries, producing subacute or chronic granulomatous inflammatory masses in the wall of the caecum, right colon, and less often the small intestine or elsewhere in the colon. Rarely, the predominant feature is ischaemic infarction. The finding of an adult nematode measuring 18 to 42 mm in length within a gut arterial vessel is diagnostic of infection; eggs may be seen in vessels or in tissue, where they are surrounded by eosinophil granulomas. Lesions also occur in regional abdominal lymph nodes or the omentum. Some larvae enter the hepatic artery and cause granulomatous or necrotic lesions in the liver; others enter testicular arteries causing similar lesions of the testis. In a recently reported case an adult worm was shown histologically within a hepatic arteriole.

Clinically, most patients present with right-sided or right iliac fossa pain, with tenderness and sometimes a palpable mass in this region. Other features are eosinophilia, fever, diarrhoea, or rectal bleeding. Tender hepatomegaly with high blood eosinophilia occurs in some patients. Serious complications are bowel obstruction and perforation, and rarely testicular infarction.

Diagnosis and treatment

The confirmation of diagnosis is usually made histologically on resected material. The condition can mimic appendicitis, bowel neoplasm, Meckel’s diverticulitis, testicular torsion, or other surgical problems. Parasite eggs are not found in faeces, but serology using enzyme immunoassay or latex agglutination is useful. Contrast radiology reveals filling defects and altered motility of the terminal ileum, caecum, or ascending colon. Laparoscopy can reveal the bowel and hepatic lesions; biopsy may be diagnostic.

The value of anthelmintic treatment remains unproven; tiabendazole or high doses of mebendazole have been used. Surgery is often necessary, but can sometimes be deferred in uncomplicated cases when the diagnosis is strongly suspected, as spontaneous remission is common.

Preventive measures include washing and careful inspection of vegetables, and hand washing before meals by children and those preparing salads. Rinsing salads in 1.5% bleach kills larvae.