Neurological symptoms in occult neurocysticercosis after single taeniacidal dose of praziquantel.
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Biomedical subjects
Publications and source records attributed to A Flisser.
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A dipstick dot ELISA for detection of Taenia-specific coproantigens was developed. The test was based on a sandwich ELISA using antibodies raised against adult Taenia solium. Antibodies were absorbed to nitrocellulose paper previously adhered to acetate plastic to form dipsticks. Once blocked with 5% skimmed milk and dried the antibody-coated dipsticks were stable for several weeks at room temperature. Both micro and dot ELISA formats were genus specific although the dot ELISA was less sensitive than the micro ELISA based on the same antiserum. During field studies, in which the majority of samples were tested in rural villages soon after collection, 3728 samples were tested. All samples were also examined by microscopy using formol ether concentration and individuals questioned to determine whether they were aware of being infected. After the initial diagnostic work individuals were treated with taeniacidal drugs for worm recovery. Use of the coproantigen test significantly increased the number of cases diagnosed. Of the 41 cases diagnosed by the three diagnostic techniques combined 31 were detected by the dipstick assay making it the most sensitive technique employed. The specificity of the dipstick assay was 99.9% with a positive predictive value of 88.6%. The combined diagnostic approach did not, however, diagnose all cases. The coproantigen test was fast and easy to use. Further improvements may make the dipstick test suitable for wide-scale use in field studies and diagnostic laboratories.
BACKGROUND AND METHODS: From June 1990 through July 1991, intracerebral infection with the larval stage of the pork tapeworm Taenia solium was diagnosed in four unrelated persons in an Orthodox Jewish community in New York City. None of the patients had eaten pork, and only one had traveled to a country in which T. solium infection was endemic. We investigated this outbreak, screened serum samples from family members and household contacts for antibodies to cysticercosis, and examined stool specimens from household employees for eggs of taenia species. RESULTS: The four patients had recurrent seizures and brain lesions that were radiologically consistent with the presence of cysticerci. The diagnosis was confirmed in two patients by a brain biopsy, and in two by immunoblot assays for cysticercus antibodies. Of 17 immediate family members screened serologically, 7 from two families had cysticercus antibodies. Magnetic resonance imaging of the brain showed cystic lesions in two of the seropositive family members, one of whom had had a seizure. Examinations of six domestic employees from all four households revealed an active infection with taenia species in one and a positive serologic test in another. Since these women had recently emigrated from Latin American countries where T. solium infection is endemic, they were the most likely sources of infection in the members of these households. CONCLUSIONS: A diagnosis of neurocysticercosis should be considered in patients with seizures and radiologic evidence of cystic brain lesions, even in those who do not eat pork and who have not traveled to a country in which T. solium infection is endemic. Recent emigrants from countries in which T. solium infection is endemic should be screened for tapeworm infection in their stools before they are employed as housekeepers or food handlers.
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In a Mexican village in which Taenia solium infection was known to be endemic, we selected a cluster sample of 368 households (21% of the total) for demographic, environmental, and diagnostic surveys, and medical histories for taeniasis and cysticercosis. Coproparasitologic studies of 1,531 participants revealed infection by Taenia sp. in four (0.3%) individuals; however, 5.8% of the respondents reported a history of having passed tapeworm proglottids in feces. Of 1,552 human serum specimens, 10.8% tested positive in the cysticercosis immunoblot assay. Seropositivity increased with age and reached a maximum in subjects ages 46-55 years. Risk factors associated with seropositivity included a history of passing tapeworm proglottids, frequent consumption of pork, and poor personal and household hygiene (P less than 0.05). A history of seizures was also significantly associated with seropositivity (P less than 0.05); approximately one-third of persons with such histories were seropositive. Of 571 pigs examined by tongue inspection, 23 (4.0%) had cysticerci; infection rates increased with the age of pigs, and were higher in pigs that habitually ran loose or were fed human feces (P less than 0.05). Goodness of fit analysis confirmed that seropositive persons (but not infected pigs) were significantly clustered within households, particularly, in households in which a member reported a history of having passed tapeworm proglottids. The results of this study have identified community behavioral and environmental practices that must be modified to prevent continued transmission of cysticercosis and taeniasis.
We found the following results in 30 patients with intraocular cysticercosis: (1) a higher incidence in the first two decades of life compared with neurocysticercosis, (2) living cysticerci concomitant with inflammatory reactions, (3) diseases related to immune dysfunction in 17% of the cases, (4) anticysticercus antibodies in 57% of cases, (5) blindness in 81% of patients despite proper surgery, and (6) adult Taenia solium infection in a higher frequency of cases than expected for the Mexican population. We discuss these findings in light of recent and established knowledge regarding this disease.
The in vitro effect of Praziquantel (PZQ) on Taenia solium cysticerci was analyzed. The oxygen consumption rate of the parasites was inhibited and the release of proteins was enhanced, but no statistically significant differences were found between the control group and the experimental groups. The drug had a significant, dose-dependent negative effect on the evagination ability of the larvae; 50% effect was seen at concentrations of between 10(-9) and 10(-8) M PZQ. The drug also induced morphological disturbances in the tegument of the worm and of the bladder wall. Finally, a very drastic effect was the induction of spastic paralysis in evaginated cysticerci at high drug doses and of flaccid paralysis at lower PZQ concentrations. The dose inducing these effects was various orders of magnitude lower than that inhibiting the evagination ability of intact cysts. Moreover, the latter effect was reversible after had been washed out the drug and the parasites had been cultured. We suggest that PZQ alters the Ca2+ flux in T. solium as it does in other helminths. Furthermore, we corroborated the protective role of the bladder for the invaginated worm. Finally, we think that in vivo the drug must act synergistically with the immune system components so as to eliminate the parasite.
The effect of the host's inflammatory capsule or of physical restraint on the spontaneous evagination capacity of Taenia solium cysticerci was evaluated. Parasites obtained from infected pig muscle, in which the surrounding inflammatory capsule was not eliminated, were unable to evaginate spontaneously after 12 or 60 h of culture. This phenomenon was not abolished when the capsule was eliminated and the parasites were cultured in semi-solid agar or in liquid medium.
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A round table of international scientists was held to discuss status of research on parasitism and diseases caused by larval cestode infections. The principal species discussed included Echinococcus granulosus and E. multilocularis, etiological agents of the cystic and alveolar forms of hydatid disease, respectively, and Taenia solium, the cause of cysticercosis. Recent advances in research include new experimental models, methods of in vitro culture, methods of immunodiagnosis, a vaccine, and new approaches to epidemiological investigation and control. Considerable progress has been achieved in the development of chemotherapy for larval cestode diseases, however, many questions and issues related to indications for and evaluation of treatment remain unresolved. Application of modern biotechnology in these diseases have produced many new diagnostic, therapeutic and prevention tools and a major current challenge is to make these available for clinical and field application, including control programs. The use of different methods--from the classical morphological one to the recently DNA based technologies--for differentiation of new strains, and most importantly, the use of these modern molecular methods for comparing antigens with potential vaccinating abilities against the different strain/species, was highlighted during this round table.
Cysticercosis is caused by the establishment of Taenia solium larvae in the central nervous system, skeletal muscle and eyes of humans and pigs, after ingestion of eggs shed in human feces by the adult tapeworm. Human cysticercosis is increasingly recognized as a public health problem, especially in developing countries, and swine cysticercosis may be an important economic drain to the meat industry. The adult tapeworm is found only in human beings. Recent epidemiological data indicate that the presence of a tapeworm carrier in the close environment is a greater risk factor for acquiring cysticercosis than the spread of eggs through sewage.
Porcine Taenia solium cysticercosis, recognized as a model of the human disease, was used to analyze the effect of the anthelminthic drug praziquantel on hosts and parasites. The drug (50 mg/kg daily) was given over 15 days in the feed of 13 cysticercotic and 9 control pigs. Changes in the number, size and appearance of brain parasites were seen by computerized tomography immediately after the last dose of praziquantel, although not all cysticerci had disappeared by day 47 following the end of the treatment. Muscle parasites became small and hyperdense shortly after treatment and disappeared from tomographic images afterwards. No alterations were found in EEGs or in brain-stem auditory and somatosensory evoked potentials. Muscle cysticerci showed increasing degrees of degeneration with time after treatment, and an augmented inflammatory reaction was concomitantly observed. In contrast, more heterogeneous results were obtained in parasites lodged in the brain, since viable cysts and less intense inflammatory reactions were found in the brain at different times after treatment. Physiological evaluation of the parasites showed that evagination was inhibited immediately after treatment and that oxygen consumption decreased with time. The results of this investigation suggest that praziquantel damages cysticerci and that the inflammatory reaction destroys and eliminates them.
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Immunodiagnostic tests for Taenia-specific faecal antigen based on polyclonal rabbit antisera against Taenia saginata or Taenia solium proglottid extracts in capture-type ELISA assays have been developed. Taenia-specific antigen was detected in detergent-solubilized faecal extracts from T. solium- and T. saginata-infected hosts. Coproantigen from T. solium-infected hamsters did not cross-react with faeces from rodents infected with Hymenolepis diminuta, H. citelli, H. microstoma, Necator americanus, Strongyloides ratti or Nematospiroides dubius and faeces from uninfected animals. When the T. saginata-capture ELISA was tested with faecal samples positive for T. solium antigen, no cross-reactions were obtained. However, faecal samples from humans infected with T. solium or T. saginata, including some with extremely low egg counts, were cross-reactive by either test. Nevertheless, considerably higher O.D. values were obtained with stool samples from Taenia patients compared to Hymenolepis nana-infected or uninfected individuals. Two individuals, infected with Taenia sp. and positive for coproantigens by ELISA, became antigen-negative 6 days after treatment with Niclosamide. The possibility of developing species-specific immunodiagnostic tests for human taeniasis through coproantigen detection is discussed.
Taenia solium cysticercosis is now recognized as a priority in Mexico and a number of other developing countries, both in public health and in economic terms. Recognition of the problem has been greatly aided in recent years by new developments in molecular diagnostics. In this paper data are presented on ELISA for the detection of anti-cysticercus antibodies and of parasite antigens in patients with neurocysticercosis and in cysticercotic pigs. Also, several biological fluids were evaluated: cerebrospinal fluid (CSF), serum and saliva, all of which have proved useful. CSF is, however, the most appropriate for detection of antibodies and antigens in patients and serum in pigs. In addition, saliva may be especially used in epidemiological surveys. The electroimmuno-transfer blot technique (EITB) for antibody detection in patients and pigs has also proved highly sensitive and due to the use of an enriched fraction of glucoproteins, EITB is also highly specific. Cloned cDNA sequences from T. solium are now being assessed as an alternative source of antigens for immunodiagnosis. Two methods for the diagnosis of the adult stage of T. solium are also undergoing standardization. These are an ELISA for the detection of parasite antigens in fecal samples and DNA hybridization techniques for the detection of eggs in stools. Both assays have promising results and should now be assessed in larger numbers of clinical and epidemiological samples.
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An experimental model of Taenia crassiceps intraocular cysticercosis was developed in rabbits. The objectives of this study were to analyze the pathophysiology of this parasitic infection and to evaluate the humoral immune response. Cysticerci, inoculated in the anterior chamber of the eye, were able to grow; no inflammatory changes in the eye or anticysticercus antibodies in serum or in aqueous humor were detected during the 12-day period. In contrast, rabbits that had previously been either infected intraperitoneally with living T. crassiceps cysts or immunized intramuscularly with T. crassiceps antigenic extract developed an intense inflammatory reaction in the eye and high levels of antibodies were detected in serum and aqueous humor even before the intraocular inoculation of parasites. Furthermore, intraocular cysticerci showed minimal growth and some were eliminated. These findings support the concept that the eye is an immunologically privileged site in the nonimmunized host and the importance of the immune response in the elimination of this parasitic infection.
Compressed organ autoradiography has been used to determine whether the anthelmintic drug praziquantel (Pzq) modifies the migration of isotopically labelled Schistosoma mansoni during the first 16 days of infection in CBA/Ca mice. The mice were treated with 500 mg kg-1 body weight of the drug on day 1 or day 6. Treatment caused a marked delay in parasite migration from the skin when the drug was administered intradermally at the site of infection on day 1; migration from the lungs was also delayed after such treatment. Pzq injected either intradermally on day 1 or intramuscularly on day 6 effectively reduced the number of parasites that finally arrived in the lungs and the livers by 41 and 47%, respectively. Intramuscular administration of the drug on day 1 had a negligible effect. Worm recoveries assessed on day 38 by perfusion of the hepatic portal system were greatly reduced when Pzq was administered on day 14. The worms proved less susceptible when the drug was administered on day 21 and were completely resistant following drug delivery on day 28. The influence of drug preparation and route of delivery on parasite migration and survival are discussed.