An Outbreak of Eosinophilic Meningitis in a Group of Travelers to Jamaica
Special Feature
The division of parasitic diseases, national center for infectious Diseases, CDC, has been assisting the Chicago Department of Public Health, Arizona health officials, the Caribbean Epidemiology Centre (CAREC), Northwestern University and the Ministry of Health, Jamaica, in their investigation of an outbreak of eosinophilic meningitis thought to be caused by Angiostrongylus cantonensis. A group of 23 tourists from Chicago and other cities in the United States traveled together to Jamaica April 2-9, 2000. Eleven (47.8%) of the 23 tourists have developed symptoms and signs of meningitis a median of 10 days after leaving Jamaica (range, 5-20 days). Nine of the tourists have been hospitalized; eight had eosinophils in their cerebrospinal fluid (CSF) (range, 3-48%). Chief complaints from patients have included headache, neckache, backache, nausea, visual disturbances, nuchal rigidity, paresthesias, and hyperesthesias. Three patients have required steroids to treat severe headaches. No antihelminthics were used for treatment. No patient has died. Serologic testing done in Thailand has revealed positive Western blot for Angiostrongylus sp. in five patients so far. Cases are still being sought and interviews are being conducted to identify the route of infection.
Comment by Michele Barry, MD, FACP
The entity of eosinophilic meningitis can be defined by the presence of greater than 10 eosinophils/mL CSF and/or 10% or greater eosinophilia among CSF leukocytes from a patient presenting with clinical signs of meningitis.1 Although the eosinophil’s bilobed nucleus and prominent cytoplasmic granules may be distinguished from other leukocytes in an unstained CSF sample, a more reliable approach is examination of a centrifuged CSF preparation stained with Wright’s or Giemsa stain to quantitate the numbers of eosinophils within the CSF.
Etiology and Epidemiology
Although eosinophilic meningitis can occur in a variety of conditions such as parasitic diseases, myeloproliferative diseases, foreign bodies, and miscellaneous conditions (see Table), the most common worldwide cause of eosinophilic meningitis is invasion of the human CNS by the rat lungworm, Angiostrongylus (Parastrongylus) cantonensis.2 Discovered in rat lungs by Chen in Canton, China, in 1935, human infection has been reported from islands of the South Pacific, Australia, Malaysia, India, Indonesia, Papua New Guinea, Thailand, Guam, Vietnam, Madagascar, Réunion, Ivory Coast, Egypt, Hawaii, Puerto Rico, and Cuba. The most recent outbreak of eosinophilic meningitis from Jamaica has been preliminarily attributed to A. cantonensis. Ship-borne intercontinental dissemination of infected rats has been implicated in the distribution of A. cantonensis from its primary endemic locations in the Pacific Basin and Southeast Asia to the Americas.
| Table-Causes of Eosinophilic Meningititis |
Differential Diagnosis: Parasitic Causes of Eosinophilic Meningitis
The three most common parasitic causes of eosinophilic meningitis are A. cantonensis, Gnathostoma sphingerum, and Baylisascaris procyonis. Less common parasitic diseases described in case reports to cause CSF eosinophilia and occasional clinical signs of meningitis include: cerebral and spinal schistosomiasis, rare cases of neurocysticercosis, cerebral or spinal paragonimiasis, fascioliasis with ectopic CNS localization, migrating CNS ascaris, CNS strongyloidiasis, CNS echinococcus, migrating larvae of Toxocara and Trichinella spp., and disseminated Onchocerca volvulus. CSF eosinophilic counts in these less common parasitic causes of eosinophilic meningitis are usually lower than seen in cases caused by the three most common parasites.
Angiostrongylus Eosinophilic Meningitis
There are 20 species of the nematode Angiostrongylus that infect animals but only three species are believed to cause eosinophilic meningitis in humans; A. cantonensis (the most common cause), A. malaysiensis, and A. mackerrasae. Recently, based on morphology, A. cantonensis has been transferred to the genus, Parastrongylus.2
Pathogenesis
Adults of the rat lungworm, A. cantonensis reside within and lay their eggs in the pulmonary arteries of rats. After hatching, larvae migrate out of the respiratory tract, are swallowed, and pass out with feces. They develop into second- and third-stage larvae within their natural intermediate hosts, slugs and snails. Freshwater prawns, land crabs, and frogs (paratenic or transport hosts) have been found to harbor third-stage larvae as well, presumably as a result of eating intermediate hosts. Humans become infected when ingesting infected mollusks, including freshwater crabs and shrimp, and unwashed ground vegetation such as watercress or lettuce where infected small slugs can be inadvertently eaten or contaminate vegetation with infected slime.
Clinical Presentation
Larvae of A. cantonensis are neurotropic and clinical manifestations of CNS infection occur 2-35 days after ingestion of larvae. The disease usually presents as a transient meningitis with excruciating headache, neck stiffness, nausea, and vomiting. Severe peripheral parasthesias are distinctive complaints and may persist for weeks after other symptoms resolve. Cranial nerve involvement, especially of the facial nerve, and visual disturbances rarely occur but urinary retention, ataxia, and spinal cord lesions are rare. Fever rarely exceeds 38ºC. Other clinical findings include abdominal discomfort, generalized weakness, flaccid paralysis of extremities, optic atrophy, periorbital edema, and pulmonary symptoms. The duration of illness ranges from 2-8 weeks. Most cases resolve without serious neurologic sequelae. Investigators of the Jamaica outbreak described excruciating headache, paresthesias, and hyperesthesias as striking in these clinical presentations.
Laboratory Diagnosis
CSF examination reveals leukocyte counts, which range from 20-5000 cells (usually 150-2000);1 CSF eosinophilia is usually in the range of 20-70% with normal or minimally low glucoses and slightly elevated CSF protein. Peripheral blood eosinophilia does not correlate with CSF eosinophilia and is usually somewhat abnormal. Larvae are rarely recovered from the CSF antemortem, but Western blot serologic testing and enzyme-linked immunoassay testing can be obtained to confirm the diagnosis. Predominately, diagnosis is based on the clinical presentation of CSF eosinophilia, exposure history, and the lack of focal lesions on CT or MRI. Other parasitic causes of eosinophilic meningitis such as gnathostomiasis, neurocysticercosis, baylisascaris infection, or infections caused by other migrating larvae usually cause focal abnormalities on CT or MRI scan.
Management and Treatment
As A. cantonensis cannot complete its life cycle in humans; larvae usually die within 1-2 weeks and most patients recover without sequelae. Nonsteroidal anti-inflammatory agents and (occasionally) narcotics are used for headache. Although corticosteroids and repeated lumbar punctures have been used with some success in cases with increased intracranial pressure, no controlled studies have been performed.2 Thiabendazole, mebendazole, and ivermectin have been reported to kill migrating A. cantonensis larvae in infected rodents, but only rarely have nonenthusiastic case reports describing its use in humans been reported. The Medical Letter cautions that using antiparasitic drugs can provoke neurologic symptoms. One report described treatment of two patients in New Hebrides with thiabendazole and both patients became markedly more symptomatic with treatment. Surgical removal of larvae is recommended for patients with ocular involvement.
Prevention and Control
Prevention is accomplished by educating travelers or persons in endemic areas that snails, slugs, freshwater shrimp and crabs must be cooked, not simply marinated. Vegetables must be thoroughly washed prior to eating. Commonly infected mollusks like the giant African land snail should not be handled or eaten. Control of rats in endemic areas or on ships is an important adjunct control measure.
Conclusion
Watch for travelers from Jamaica who present with unresolved headaches, paresthesias, or clinical signs of aseptic meningitis. A lumbar puncture revealing striking eosinophilia can confirm your suspicion of Angiostrongylus infection. Report any suspicious case to Dr. Barbara Herwaldt, at the CDC (telephone: 770-488-7772).
References
1. Weller P. Eosinophilic meningitis. Am J Med 1993;95(3):250-253.
2. Koo J, Pien F, Kliks M. Angiostrongylus (Parastrongylus) eosinophilic meningitis. Rev Infect Dis 1988; 10(6):1155-1162.
Editor’s Note
A special note of appreciation for the comments offered by Drs. B. Herwaldt and Susan Gerber concerning the Jamaica outbreak of eosinophilic meningitis.
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