Tapeworms and Seizures — Treatment and Prevention
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《新英格兰医药杂志》
It may come as a surprise that a lowly tapeworm is responsible for as many as 10 percent of cases in which a patient presents with seizures to an emergency room in a large urban hospital in New Mexico or California. In fact, cysticercosis, infection with the larval stage of the pork tapeworm, Taenia solium, is the most common parasitic disease of the central nervous system worldwide, and it is the leading cause of late-onset epilepsy in many developing countries. Most of the estimated 50 million cases of cysticercosis originate in poor communities of Latin America, Asia, and Africa, but seizures and other complications of neurocysticercosis are not uncommon in industrialized countries because of increasing rates of travel and immigration.
Cysticercosis is acquired by ingesting microscopic taenia eggs that are shed in the stools of persons infected with an adult tapeworm. In the gut of the host, the eggs release embryonic larvae that travel through the bloodstream to various organs, where they develop into fluid-filled cystic larvae within months. Neurocysticercosis is the most serious complication; cysticerci in locations other than the central nervous system or eye rarely cause harm. Mature cysts in the parenchyma of the brain measure about 1 to 2 cm in diameter but cause no symptoms as long as they remain viable, which they typically do for a period of years. Living cysts successfully evade the host's immune defenses, but the inflammation that is provoked by a dying parasite can trigger a seizure. Calcifications often develop as the inflammatory nodule disappears, and they can act as a focus for recurrent seizures.
Antiparasitic drugs that kill cysticerci have been available since 1978, but their use in the treatment of persons with viable cysts and seizures is controversial. Proponents of anticysticercal treatment argue that the elimination of cysts reduces the risk of recurrent seizures and that the complications of cyst death can be managed better in a controlled situation (with antiinflammatory drugs and anticonvulsants) than when cysts die naturally and therefore unpredictably. Opponents point out that cysts often die without causing symptoms and that antiparasitic treatment may enhance the development of scars and calcifications that lead to chronic seizures. Previous clinical trials have yielded conflicting results concerning the occurrence of seizures and the disappearance of cystic lesions in the treated and untreated groups.
In this issue of the Journal, Garcia and colleagues (pages 249–258) present strong evidence in support of anticysticercal treatment. Their well-designed randomized, placebo-controlled trial focused on the most common complication of neurocysticercosis — seizures in the presence of small-to-moderate numbers of viable parenchymal cysticerci. Patients who received a 10-day course of the anthelmintic agent albendazole in addition to dexamethasone and anticonvulsants had fewer seizures and more rapid resolution of cysts than persons who received only anticonvulsants and placebos. Treatment with albendazole was safe: with the exception of abdominal pain, side effects were similar in the two groups. As expected, more patients in the albendazole group than in the placebo group had seizures during treatment and during the first month after treatment, but by 2 months this trend had reversed, and a trend toward a higher rate of seizures in the placebo group persisted for the rest of the 18 months of follow-up.
As the authors emphasize, the treatment was not completely effective. The number of patients who became free of seizures was similar in the two groups, and the reduction in the number of seizures among patients who received the treatment was significant only with respect to seizures with generalization, not with respect to partial seizures. These findings do not diminish the value of the study, however, since frequent seizures and generalized seizures have the greatest effect on the quality of life. Further studies are needed to determine whether longer or repeated courses of therapy will render more patients free of seizures and leave patients with fewer remaining cysticerci. It is important to realize that the results do not apply to persons with other, less common forms of cysticercosis, such as numerous or giant cysticerci that cause mass effect and intraventricular or subarachnoid cysticerci that can cause hydrocephalus, stroke, and chronic meningitis.
Although the study by Garcia et al. represents an important advance in the management of neurocysticercosis, it will benefit only patients who have access to sophisticated medical care. Most affected people live in poor countries and do not have access to computed tomography, magnetic resonance imaging, or reliable serologic tests, which are necessary for the detection of cysticerci in the brain or for confirmation of the diagnosis. For this reason, prevention is a priority, and there are measures that effectively interrupt transmission at every stage of the cycle (see Figure). Each case of cysticercosis has as its source a person who harbors an adult tapeworm. Although tapeworms reach lengths of 3.7 m (12 ft) or longer, most carriers are asymptomatic and may unwittingly transmit cysticercosis to members of their households if hygiene is lax. Patients anywhere in the world who have cysticercosis and the members of their households should be examined for tapeworms. Persons who are found to be infected should be treated with a single dose of niclosamide or praziquantel.
Figure. Taeniasis and Cysticercosis — Life Cycle and Interventions.
The dashed lines represent the points at which a given intervention can interrupt the cycle.
Efforts to prevent taeniasis (infection with the adult tapeworm) focus on pigs and pork. Pigs that are allowed to roam and forage freely acquire cysticerci by consuming tapeworm segments and eggs shed by tapeworm carriers that contaminate the environment with their feces. Humans acquire adult tapeworms by eating uncooked or poorly cooked pork that contains cysticerci. Hence, the transmission of taeniasis occurs in settings where sanitation is inadequate and where poor, rural families depend on pigs as an inexpensive and practical source of income. Because a cysticercotic pig represents a loss of income, farmers avoid having their animals inspected before they sell them.
Taeniasis was eliminated in industrialized countries through improved sanitation and the commercialization of large-scale swine raising, with strict control of herds and inspection of pork. In 1992, the International Task Force for Disease Eradication listed cysticercosis as one of only six potentially eradicable infectious diseases. The temporary interruption of transmission with the use of multiple interventions has already been demonstrated in several small, rural villages in Latin America. The sustained interruption of transmission will be facilitated by important recent advances, including new diagnostic tests for infection in pigs and humans, a drug that kills cysticerci in pigs and renders them resistant to reinfection, and a vaccine to prevent infection in pigs. Fair reimbursement for infected pigs will prevent farmers from bypassing formal inspection channels. Large demonstration projects are planned in order to demonstrate the feasibility of elimination at national levels, but even in the absence of elimination, we have the tools to achieve great reductions in morbidity due to cysticercosis. What is required now is the commitment and will on the part of the international community to use these tools.
Source Information
From the Parasitic Disease Epidemiology Branch, Centers for Disease Control and Prevention, Atlanta.(James H. Maguire, M.D.)
Cysticercosis is acquired by ingesting microscopic taenia eggs that are shed in the stools of persons infected with an adult tapeworm. In the gut of the host, the eggs release embryonic larvae that travel through the bloodstream to various organs, where they develop into fluid-filled cystic larvae within months. Neurocysticercosis is the most serious complication; cysticerci in locations other than the central nervous system or eye rarely cause harm. Mature cysts in the parenchyma of the brain measure about 1 to 2 cm in diameter but cause no symptoms as long as they remain viable, which they typically do for a period of years. Living cysts successfully evade the host's immune defenses, but the inflammation that is provoked by a dying parasite can trigger a seizure. Calcifications often develop as the inflammatory nodule disappears, and they can act as a focus for recurrent seizures.
Antiparasitic drugs that kill cysticerci have been available since 1978, but their use in the treatment of persons with viable cysts and seizures is controversial. Proponents of anticysticercal treatment argue that the elimination of cysts reduces the risk of recurrent seizures and that the complications of cyst death can be managed better in a controlled situation (with antiinflammatory drugs and anticonvulsants) than when cysts die naturally and therefore unpredictably. Opponents point out that cysts often die without causing symptoms and that antiparasitic treatment may enhance the development of scars and calcifications that lead to chronic seizures. Previous clinical trials have yielded conflicting results concerning the occurrence of seizures and the disappearance of cystic lesions in the treated and untreated groups.
In this issue of the Journal, Garcia and colleagues (pages 249–258) present strong evidence in support of anticysticercal treatment. Their well-designed randomized, placebo-controlled trial focused on the most common complication of neurocysticercosis — seizures in the presence of small-to-moderate numbers of viable parenchymal cysticerci. Patients who received a 10-day course of the anthelmintic agent albendazole in addition to dexamethasone and anticonvulsants had fewer seizures and more rapid resolution of cysts than persons who received only anticonvulsants and placebos. Treatment with albendazole was safe: with the exception of abdominal pain, side effects were similar in the two groups. As expected, more patients in the albendazole group than in the placebo group had seizures during treatment and during the first month after treatment, but by 2 months this trend had reversed, and a trend toward a higher rate of seizures in the placebo group persisted for the rest of the 18 months of follow-up.
As the authors emphasize, the treatment was not completely effective. The number of patients who became free of seizures was similar in the two groups, and the reduction in the number of seizures among patients who received the treatment was significant only with respect to seizures with generalization, not with respect to partial seizures. These findings do not diminish the value of the study, however, since frequent seizures and generalized seizures have the greatest effect on the quality of life. Further studies are needed to determine whether longer or repeated courses of therapy will render more patients free of seizures and leave patients with fewer remaining cysticerci. It is important to realize that the results do not apply to persons with other, less common forms of cysticercosis, such as numerous or giant cysticerci that cause mass effect and intraventricular or subarachnoid cysticerci that can cause hydrocephalus, stroke, and chronic meningitis.
Although the study by Garcia et al. represents an important advance in the management of neurocysticercosis, it will benefit only patients who have access to sophisticated medical care. Most affected people live in poor countries and do not have access to computed tomography, magnetic resonance imaging, or reliable serologic tests, which are necessary for the detection of cysticerci in the brain or for confirmation of the diagnosis. For this reason, prevention is a priority, and there are measures that effectively interrupt transmission at every stage of the cycle (see Figure). Each case of cysticercosis has as its source a person who harbors an adult tapeworm. Although tapeworms reach lengths of 3.7 m (12 ft) or longer, most carriers are asymptomatic and may unwittingly transmit cysticercosis to members of their households if hygiene is lax. Patients anywhere in the world who have cysticercosis and the members of their households should be examined for tapeworms. Persons who are found to be infected should be treated with a single dose of niclosamide or praziquantel.
Figure. Taeniasis and Cysticercosis — Life Cycle and Interventions.
The dashed lines represent the points at which a given intervention can interrupt the cycle.
Efforts to prevent taeniasis (infection with the adult tapeworm) focus on pigs and pork. Pigs that are allowed to roam and forage freely acquire cysticerci by consuming tapeworm segments and eggs shed by tapeworm carriers that contaminate the environment with their feces. Humans acquire adult tapeworms by eating uncooked or poorly cooked pork that contains cysticerci. Hence, the transmission of taeniasis occurs in settings where sanitation is inadequate and where poor, rural families depend on pigs as an inexpensive and practical source of income. Because a cysticercotic pig represents a loss of income, farmers avoid having their animals inspected before they sell them.
Taeniasis was eliminated in industrialized countries through improved sanitation and the commercialization of large-scale swine raising, with strict control of herds and inspection of pork. In 1992, the International Task Force for Disease Eradication listed cysticercosis as one of only six potentially eradicable infectious diseases. The temporary interruption of transmission with the use of multiple interventions has already been demonstrated in several small, rural villages in Latin America. The sustained interruption of transmission will be facilitated by important recent advances, including new diagnostic tests for infection in pigs and humans, a drug that kills cysticerci in pigs and renders them resistant to reinfection, and a vaccine to prevent infection in pigs. Fair reimbursement for infected pigs will prevent farmers from bypassing formal inspection channels. Large demonstration projects are planned in order to demonstrate the feasibility of elimination at national levels, but even in the absence of elimination, we have the tools to achieve great reductions in morbidity due to cysticercosis. What is required now is the commitment and will on the part of the international community to use these tools.
Source Information
From the Parasitic Disease Epidemiology Branch, Centers for Disease Control and Prevention, Atlanta.(James H. Maguire, M.D.)