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Diagnosis and reasoning

This returning traveler has presented with a high fever, headache, and photophobia. Examination shows neck stiffness, positive Kernig and Brudzinski signs, and a positive jolt accentuation test. This should be considered to be a central nervous system (CNS) infection until proven otherwise. A lumbar puncture is an essential next step. Blood cultures should be obtained in parallel, while empirical antibiotic therapy should be commenced as soon as samples have been obtained. Note also that preceding computed tomography (CT) of the brain is unnecessary, as he does not meet any of the criteria which would mandate this (i.e. age over 60 years, immunosuppression, presence of a known CNS lesion, features of raised intracranial pressure, altered mentation, focal neurological deficits, new-onset seizures, or suspected subarachnoid hemorrhage). Lumbar puncture reveals a constellation of abnormal findings: a mildly increased opening pressure, along with marked eosinophilia and increased protein levels. When considered along with the presentation, this is strongly suggestive of eosinophilic meningoencephalitis. CNS eosinophilia is most often due to helminthic infections. Given the travel history, angiostrongyliasis and gnathostomiasis are the main considerations in this regard. Neurocysticercosis, the other major parasitic cause of CNS eosinophilia, is unlikely to present so soon after travel to an endemic area. Fungal infections, while a less common cause of eosinophilic meningoencephalitis, should not be forgotten. Cryptococcosis is the key etiology in this respect. However, this is ruled out by the negative CSF serology for the cryptococcal antigen. Few laboratories are able to test for angiostrongyliasis, and none in the United States can do so for gnathostomiasis. While the centers for disease control (CDC) perform rapid polymerase chain reaction (PCR) testing for the former, this will take time. Until then, neuroimaging is useful for differentiation. In angiostrongyliasis, magnetic resonance imaging (MRI) shows no abnormal findings or only nonspecific findings. In gnathostomiasis, intracerebral hemorrhages, non-traumatic subdural hematomata, and unexplained subarachnoid hemorrhages are common. However, none of these findings are present in this patient's MRI, making angiostrongyliasis the probable diagnosis. Angiostrongyliasis is self-limiting. Supportive therapy is the mainstay of management. This includes analgesics for pain control, and corticosteroids to limit the inflammation. If significant CNS hypertension develops, therapeutic lumbar punctures may also be required. Anthelmintics should be avoided, as the sudden mass death of parasites may exacerbate the inflammatory response. Antifungals would have been indicated if cryptococcosis were the likely etiology.


Angiostrongyliasis is caused by the nematode Angiostrongylus cantonensis, commonly termed the "rat lungworm". Detailed epidemological data is scant. However, the infection is mainly found in Southeast Asia and the islands of the Pacific. Cases have also been described in Australia, areas of Africa, the Caribbean, Hawaii, Louisiana, and islands of the Indian Ocean. Due to international travel, imported cases are also increasingly encountered in non-endemic countries. The adult parasites live in the pulmonary arteries of rats. The females lay eggs which hatch into first-stage larvae. These larvae migrate to the pharynx and are swallowed. They then pass along the gastrointestinal tract, and are excreted in feces. Molluscs are the intermediate host. These are penetrated by the larvae, which moult twice inside them to become third-stage larvae, which are infective to mammals. When the infected mollusc is ingested by the definitive mammal host, the parasites migrate to its brain and develop into young adults. They then travel to the pulmonary artery for sexual maturation, thus completing the parasite lifecycle. Humans are incidental hosts of A. cantonenesis. Infections occur after eating molluscs or paratenic hosts (such as land crabs, frogs, or freshwater shrimps) that contain or are contaminated by the third-stage larvae. Once inside the body, the parasite typically migrate to the brain and the eyes. They are unable to complete their lifestyle, eventually dying there. Their presence in the meninges and brain parenchyma causes an eosinophilic meningoencephalitis, along with increaseed intracranial pressure. Symptoms occur between a week to a month following exposure. These include acute headache, vomiting, fever, neck stiffness and migrating paraesthesia. Where there is direct larval invasion of the ocular structures, diplopia and visual disturbances may occur. Radicular pain, potentially with hyperesthesia in the same distribution is a less common manifestation. Motor weakness and focal neurological deficits are rare. Complete blood counts may show peripheral eosinophilia. Cerebrospinal fluid (CSF) findings include increased opening pressure, a cloudy appearance, elevated protein but normal glucose levels, and an elevated white cell count with eosinophilia. Neuroimaging studies may be normal. Where present, they are usually non-specific. MRI findings include micronodular enhancement of the brain parenchyma and linear enhancements in the pia mater. Serological tests, molecular diagnostic tests and immunoassays can be used for diagnosis, but are not widely available. Antibody detection systems may fail to detect early infections, as animal studies have shown peak antibody levels are only reached four weeks after infection. Angiostrongyliasis is self-limiting, with symtoms resolving within several weeks. Supportive treatment is the mainstay of management. This includes analgesics, prednisolone to control the inflammatory response, and serial lumbar punctures to decrease the intracranial pressure. The use of anti-helminthic agents such as albendazole is controversial. Studies show that they may help alleviate symptoms and shorten the course of disease, but with the risk of exacerbating the inflammation and worsening the symptoms. Combination therapy with prednisolone has been investigated, with certain studies demonstrating promising results. If the parasites invade the eyes, surgery is indicated to remove the worms to prevent further damage. Public education against the consumption of raw or undercooked slugs, snails, and other paratenic animals such as land crabs and frogs is also important to reduce the risk of infections. Due to the self-limiting nature of the disease, permanent neurological damage is rare, and mortality even rarer. However, prompt treatment is necessary in persons with severe disease, so as to prevent deterioration and even death.

Take home messages

  1. Angiostrongyliasis is the most common cause of eosinophilic meningitis.
  2. The infection is associated with the consumption of raw or undercooked molluscs in endemic regions.
  3. The vast majority of cases are self-limiting, resolving spontaneously in several weeks.
  4. Supportive therapy is the mainstay of management. The use of anti-helminthic agents is controversial, due to the risk of worsening symptoms.

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