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Parasitic Brain Disease Crosses the Border

Figure 1

An intestinal parasite that has long existed in Mexico and nations to the south is being imported into the U.S. with increasing frequency. Taenia solium, the organism that gives rise to intestinal tapeworms from eating undercooked pork, also causes the lesser-known disorder called neurocysticercosis. Whereas the larval stage of T. solium produces tapeworms, neurocysticercosis occurs when people with pork tapeworms shed T. solium eggs in their feces and infect others through a fecal-oral route of transmission. Because the eggs show an affinity for brain tissue, neurological problems often result.

No one knows why the eggs favor the brain or how they get there. After ingestion, stomach acids dissolve the outer membranes of eggs and release an immature larval stage. Experts suspect that this immature larval form travels to the brain, where it grows into a mature larval form. Individuals who are infected with tapeworms can develop neurocysticercosis by eating eggs that they themselves excrete. ``However, the incidence of autoinfection is lower than expected,'' says immunologist Judy M. Teale of the University of Texas Health Science Center in San Antonio, suggesting that the tapeworm provides some sort of immunity against this secondary infection that leads to central nervous system (CNS) complications.

The organism may lodge in the CNS for 3 to 10 years before symptoms appear. Some patients show no outward effects, and the disease is not discovered until an autopsy is performed. Others suffer a variety of maladies, including headaches, seizures, hydrocephalus, and psychosis, depending on the part of the brain infected. A diagnosis is made by computerized tomography scans that reveal cysts formed by the organism.

``Neurocysticercosis is the most common parasitic disease of the central nervous system worldwide,'' says Teale. The disease is endemic in rural areas of Latin America, Asia, and Africa. In Latin America, neurocysticercosis infects an estimated 5% of the population. Epidemiological studies show that neurocysticercosis is the leading cause of late-onset epilepsy in endemic areas.

The number of cases is increasing in Texas, California, and other southwestern states where immigrants import the disease with them. The exact number of cases is unknown, because ``cases of neurocysticercosis are not required by law to be reported to public health departments except in California,'' says epidemiologist Peter M. Schantz of the Centers for Disease Control and Prevention in Atlanta, Georgia. In Los Angeles County, the number of neurocysticercosis cases increased four times between 1977 and 1981 and now averages more than 100 a month, with 90% occurring in Hispanics. ``Neurocysticercosis is completely an imported disease,'' says Schantz.

However, neurocysticercosis patients given antiparasitic drugs fare worse. Killing the cysts in the brain can trigger a tremendous inflammatory response to the dead tissue. ``Patients have died from treatment,'' says Teale.

The pathology of neurocysticercosis is thought to depend on host immune responses in the brain. The organism, like other parasites, appears to trick and evade the immune system. To systematically study the immune response and find better treatments, Teale developed an animal model for this type of CNS parasitism in BALB/c mice. Because T. solium is not infectious in mice, she used an organism, Mesocestoides corti, which shows a similar life cycle. M. corti invade the CNS of mice and cause a variety of immune responses that represent early and adaptive immunity.

The immune cell types expressed in the mouse model parallel those identified in biopsies from patients with neurocysticercosis. The mice also develop neurological complications similar to those seen in neurocysticercosis patients. Future experiments will correlate neurological symptoms with immunopathology.

A striking feature of the studies is that mice produce a large number of gamma delta T-cells in response to infection by the parasite. Although gamma delta T cells ordinarily account for 5% of circulating T cells, their functions remain murky. They predominate in the skin and mucosa and appear to be frontline sentinels that produce various cytokines in response to pathogens. The gamma delta T cells that Teale is studying in mice produce interleukin-12 and trigger a Thy1 immunological response. In contrast, other parasites typically set off a Thy2 immune response. ``We don't know if this is good or bad,'' says Teale, ``but it 's certainly unusual.''

Various knockout mouse mutants are being developed to better understand the significance of the gamma delta T-cells. When the gene for gamma delta T-cells is rendered inactive in mice, interleukin-12 levels are greatly reduced and interleukin-4 levels are greatly elevated. ``We need to define the immunological response before we can find new treatments,'' says Teale.

Carol Potera
Carol Potera is a freelance science writer based in Great Falls, Mont.